Genetic Variant AHI1:c.3110-22_3110-19delTCAC (chr6-135358205-TGTGA-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001134831.2(AHI1):c.3110-22_3110-19delTCAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0084 in 1,607,222 control chromosomes in the GnomAD database, including 837 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 443 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 394 hom. )

Consequence

AHI1
NM_001134831.2 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.16

Publications

2 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 -16 ACMG points.

BP6

Variant 6-135358205-TGTGA-T is Benign according to our data. Variant chr6-135358205-TGTGA-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHI1	NM_001134831.2 link	c.3110-22_3110-19delTCAC		intron_variant	Intron 23 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.3110-22_3110-19delTCAC		intron_variant	Intron 23 of 28	1	NM_001134831.2	ENSP00000265602.6		Q8N157-1

Frequencies

GnomAD3 genomes

AF:

0.0430

AC:

6535

AN:

152144

Hom.:

441

Cov.:

show subpopulations

Gnomad AFR

AF:

0.145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0247

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000867

Gnomad OTH

AF:

0.0359

GnomAD2 exomes

AF:

0.0111

AC:

2734

AN:

247056

AF XY:

0.00856

show subpopulations

Gnomad AFR exome

AF:

0.143

Gnomad AMR exome

AF:

0.0104

Gnomad ASJ exome

AF:

0.000400

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00118

Gnomad OTH exome

AF:

0.00799

GnomAD4 exome

AF:

0.00477

AC:

6940

AN:

1454960

Hom.:

394

AF XY:

0.00418

AC XY:

3025

AN XY:

724080

show subpopulations

African (AFR)

AF:

0.144

AC:

4785

AN:

33144

American (AMR)

AF:

0.0121

AC:

539

AN:

44388

Ashkenazi Jewish (ASJ)

AF:

0.000460

AC:

AN:

26072

East Asian (EAS)

AF:

0.00

AC:

AN:

39544

South Asian (SAS)

AF:

0.000514

AC:

AN:

85616

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.0130

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.000677

AC:

749

AN:

1106954

Other (OTH)

AF:

0.0122

AC:

734

AN:

60126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

275

551

826

1102

1377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

336

504

672

840

<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:

0.0431

AC:

6557

AN:

152262

Hom.:

443

Cov.:

AF XY:

0.0423

AC XY:

3151

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.145

AC:

6039

AN:

41528

American (AMR)

AF:

0.0246

AC:

376

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000867

AC:

AN:

68012

Other (OTH)

AF:

0.0355

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

268

536

803

1071

1339

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0197

Hom.:

Bravo

AF:

0.0498

Asia WGS

AF:

0.00924

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

May 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.2

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