dbSNP rs7756167: AHI1:c.3427-1309T>C (chr6-135301867-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001134831.2(AHI1):c.3427-1309T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 985,342 control chromosomes in the GnomAD database, including 16,306 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 9963 hom., cov: 33)

Exomes 𝑓: 0.083 ( 6343 hom. )

Consequence

AHI1
NM_001134831.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.15

Publications

3 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:

ENSG00000234084 (HGNC:):

ENSG00000234084 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHI1	NM_001134831.2 link	c.3427-1309T>C		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.3427-1309T>C		intron_variant	Intron 26 of 28	1	NM_001134831.2	ENSP00000265602.6		Q8N157-1

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

36371

AN:

152164

Hom.:

9922

Cov.:

show subpopulations

Gnomad AFR

AF:

0.673

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.0427

Gnomad EAS

AF:

0.0636

Gnomad SAS

AF:

0.111

Gnomad FIN

AF:

0.0242

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0687

Gnomad OTH

AF:

0.208

GnomAD4 exome

AF:

0.0826

AC:

68822

AN:

833060

Hom.:

6343

Cov.:

AF XY:

0.0816

AC XY:

31379

AN XY:

384694

show subpopulations

African (AFR)

AF:

0.729

AC:

11497

AN:

15778

American (AMR)

AF:

0.119

AC:

117

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.0495

AC:

255

AN:

5152

East Asian (EAS)

AF:

0.0606

AC:

220

AN:

3630

South Asian (SAS)

AF:

0.104

AC:

1714

AN:

16460

European-Finnish (FIN)

AF:

0.0217

AC:

AN:

276

Middle Eastern (MID)

AF:

0.0963

AC:

156

AN:

1620

European-Non Finnish (NFE)

AF:

0.0683

AC:

52035

AN:

761864

Other (OTH)

AF:

0.103

AC:

2822

AN:

27296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

2889

5778

8667

11556

14445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.240

AC:

36473

AN:

152282

Hom.:

9963

Cov.:

AF XY:

0.231

AC XY:

17226

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.674

AC:

27956

AN:

41508

American (AMR)

AF:

0.134

AC:

2056

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0427

AC:

148

AN:

3470

East Asian (EAS)

AF:

0.0636

AC:

330

AN:

5192

South Asian (SAS)

AF:

0.109

AC:

529

AN:

4834

European-Finnish (FIN)

AF:

0.0242

AC:

257

AN:

10616

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0687

AC:

4671

AN:

68032

Other (OTH)

AF:

0.213

AC:

451

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

886

1772

2658

3544

4430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.134

Hom.:

2139

Bravo

AF:

0.267

Asia WGS

AF:

0.171

AC:

596

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.035

(source)

DANN

Benign

0.45

PhyloP100

-2.1

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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rs7756167

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over