dbSNP rs780835322: AHI1:c.2961+6_2961+7insGAC (chr6-135411341-A-AGTC) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001134831.2(AHI1):c.2961+6_2961+7insGAC variant causes a splice region, intron change. The variant allele was found at a frequency of 0.012 in 1,611,070 control chromosomes in the GnomAD database, including 139 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0098 ( 9 hom., cov: 32)

Exomes 𝑓: 0.012 ( 130 hom. )

Consequence

AHI1
NM_001134831.2 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.79

Publications

0 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 6-135411341-A-AGTC is Benign according to our data. Variant chr6-135411341-A-AGTC is described in ClinVar as [Likely_benign]. Clinvar id is 220132.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00976 (1487/152364) while in subpopulation NFE AF = 0.0141 (959/68032). AF 95% confidence interval is 0.0134. There are 9 homozygotes in GnomAd4. There are 739 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHI1	NM_001134831.2 link	c.2961+6_2961+7insGAC		splice_region_variant, intron_variant	Intron 21 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.2961+6_2961+7insGAC		splice_region_variant, intron_variant	Intron 21 of 28	1	NM_001134831.2	ENSP00000265602.6		Q8N157-1

Frequencies

GnomAD3 genomes

AF:

0.00978

AC:

1489

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00241

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.00791

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0118

Gnomad FIN

AF:

0.0147

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0141

Gnomad OTH

AF:

0.00860

GnomAD2 exomes

AF:

0.0110

AC:

2725

AN:

248044

AF XY:

0.0110

show subpopulations

Gnomad AFR exome

AF:

0.00194

Gnomad AMR exome

AF:

0.00815

Gnomad ASJ exome

AF:

0.00979

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0145

Gnomad NFE exome

AF:

0.0141

Gnomad OTH exome

AF:

0.0152

GnomAD4 exome

AF:

0.0123

AC:

17879

AN:

1458706

Hom.:

130

Cov.:

AF XY:

0.0123

AC XY:

8914

AN XY:

725680

show subpopulations

African (AFR)

AF:

0.00189

AC:

AN:

33408

American (AMR)

AF:

0.00863

AC:

385

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.00947

AC:

247

AN:

26082

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39656

South Asian (SAS)

AF:

0.0118

AC:

1013

AN:

86102

European-Finnish (FIN)

AF:

0.0139

AC:

744

AN:

53356

Middle Eastern (MID)

AF:

0.0222

AC:

128

AN:

5764

European-Non Finnish (NFE)

AF:

0.0133

AC:

14704

AN:

1109444

Other (OTH)

AF:

0.00986

AC:

594

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.424

Heterozygous variant carriers

790

1580

2370

3160

3950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

558

1116

1674

2232

2790

<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:

0.00976

AC:

1487

AN:

152364

Hom.:

Cov.:

AF XY:

0.00992

AC XY:

739

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.00240

AC:

100

AN:

41590

American (AMR)

AF:

0.00790

AC:

121

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00980

AC:

AN:

3468

East Asian (EAS)

AF:

0.000385

AC:

AN:

5194

South Asian (SAS)

AF:

0.0114

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0147

AC:

156

AN:

10624

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0141

AC:

959

AN:

68032

Other (OTH)

AF:

0.00851

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

139

209

278

348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0140

Hom.:

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Joubert syndrome

Benign:1

May 22, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Nov 26, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 31054281) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.8

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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