6-135318506-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000367799.7(AHI1):c.2491G>A(p.Glu831Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,533,058 control chromosomes in the GnomAD database, including 251,668 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 26512 hom., cov: 32)

Exomes 𝑓: 0.57 ( 225156 hom. )

Consequence

AHI1
ENST00000367799.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.0760

Publications

17 publications found

Variant links:

Genes affected

AHI1 (HGNC:21575): (Abelson helper integration site 1) This gene is apparently required for both cerebellar and cortical development in humans. This gene mutations cause specific forms of Joubert syndrome-related disorders. Joubert syndrome (JS) is a recessively inherited developmental brain disorder with several identified causative chromosomal loci. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2008]

AHI1 Gene-Disease associations (from GenCC):

Joubert syndrome 3
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Laboratory for Molecular Medicine, Ambry Genetics
Joubert syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Joubert syndrome with ocular defect
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa
Inheritance: AR, AD Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet

AHI1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 6-135318506-C-T is Benign according to our data. Variant chr6-135318506-C-T is described in ClinVar as Benign. ClinVar VariationId is 95757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHI1	NM_001134831.2 link	c.3426+13G>A		intron_variant	Intron 26 of 28	ENST00000265602.11	NP_001128303.1	Q8N157-1Q8NER0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHI1	ENST00000265602.11 link	c.3426+13G>A		intron_variant	Intron 26 of 28	1	NM_001134831.2	ENSP00000265602.6		Q8N157-1

Frequencies

GnomAD3 genomes

AF:

0.590

AC:

89578

AN:

151936

Hom.:

26484

Cov.:

show subpopulations

Gnomad AFR

AF:

0.613

Gnomad AMI

AF:

0.669

Gnomad AMR

AF:

0.606

Gnomad ASJ

AF:

0.610

Gnomad EAS

AF:

0.620

Gnomad SAS

AF:

0.533

Gnomad FIN

AF:

0.620

Gnomad MID

AF:

0.658

Gnomad NFE

AF:

0.566

Gnomad OTH

AF:

0.601

GnomAD2 exomes

AF:

0.588

AC:

107534

AN:

182890

AF XY:

0.583

show subpopulations

Gnomad AFR exome

AF:

0.616

Gnomad AMR exome

AF:

0.644

Gnomad ASJ exome

AF:

0.610

Gnomad EAS exome

AF:

0.630

Gnomad FIN exome

AF:

0.609

Gnomad NFE exome

AF:

0.562

Gnomad OTH exome

AF:

0.564

GnomAD4 exome

AF:

0.569

AC:

786425

AN:

1381004

Hom.:

225156

Cov.:

AF XY:

0.569

AC XY:

389817

AN XY:

684864

show subpopulations

African (AFR)

AF:

0.622

AC:

19865

AN:

31958

American (AMR)

AF:

0.640

AC:

24070

AN:

37638

Ashkenazi Jewish (ASJ)

AF:

0.610

AC:

15306

AN:

25110

East Asian (EAS)

AF:

0.680

AC:

25805

AN:

37930

South Asian (SAS)

AF:

0.552

AC:

43995

AN:

79696

European-Finnish (FIN)

AF:

0.597

AC:

30258

AN:

50658

Middle Eastern (MID)

AF:

0.634

AC:

3579

AN:

5648

European-Non Finnish (NFE)

AF:

0.560

AC:

590469

AN:

1054892

Other (OTH)

AF:

0.576

AC:

33078

AN:

57474

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

16391

32782

49174

65565

81956

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16584

33168

49752

66336

82920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.590

AC:

89662

AN:

152054

Hom.:

26512

Cov.:

AF XY:

0.592

AC XY:

44005

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.613

AC:

25423

AN:

41446

American (AMR)

AF:

0.606

AC:

9266

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.610

AC:

2115

AN:

3470

East Asian (EAS)

AF:

0.620

AC:

3209

AN:

5174

South Asian (SAS)

AF:

0.532

AC:

2562

AN:

4818

European-Finnish (FIN)

AF:

0.620

AC:

6554

AN:

10570

Middle Eastern (MID)

AF:

0.643

AC:

189

AN:

294

European-Non Finnish (NFE)

AF:

0.566

AC:

38469

AN:

67978

Other (OTH)

AF:

0.599

AC:

1265

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1929

3858

5787

7716

9645

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

760

1520

2280

3040

3800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.578

Hom.:

45950

Bravo

AF:

0.594

Asia WGS

AF:

0.586

AC:

2040

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 02, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 23, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joubert syndrome 3

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Joubert syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.0

(source)

DANN

Benign

0.30

PhyloP100

0.076

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over