Genetic Variant NM_032119.4:c.12121-1013G>A (chr5-90762292-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_032119.4(ADGRV1):c.12121-1013G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 151,904 control chromosomes in the GnomAD database, including 31,988 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 0.64 ( 31988 hom., cov: 32)

Consequence

ADGRV1
NM_032119.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00600

Publications

3 publications found

Variant links:

Genes affected

ADGRV1 (HGNC:17416): (adhesion G protein-coupled receptor V1) This gene encodes a member of the G-protein coupled receptor superfamily. The encoded protein contains a 7-transmembrane receptor domain, binds calcium and is expressed in the central nervous system. Mutations in this gene are associated with Usher syndrome 2 and familial febrile seizures. Several alternatively spliced transcripts have been described. [provided by RefSeq, Jul 2008]

ADGRV1 Gene-Disease associations (from GenCC):

Usher syndrome type 2
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Usher syndrome type 2C
Inheritance: AR Classification: STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
febrile seizures, familial, 4
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
nonsyndromic genetic hearing loss
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ADGRV1 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=-1.02).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.12121-1013G>A		intron_variant	Intron 58 of 89	ENST00000405460.9	NP_115495.3	Q8WXG9-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADGRV1	ENST00000405460.9 link	c.12121-1013G>A	intron_variant	Intron 58 of 89	1	NM_032119.4	ENSP00000384582.2	Q8WXG9-1
ADGRV1	ENST00000425867.3 link	c.1075-1013G>A	intron_variant	Intron 6 of 37	5		ENSP00000392618.3	A0A1X7SBU6
ADGRV1	ENST00000639431.1 link	n.265+86083G>A	intron_variant	Intron 2 of 4	5		ENSP00000491057.1	A0A1W2PNS5
ADGRV1	ENST00000640464.1 link	n.2540-1013G>A	intron_variant	Intron 15 of 20	5

Frequencies

GnomAD3 genomes

AF:

0.641

AC:

97306

AN:

151786

Hom.:

31950

Cov.:

show subpopulations

Gnomad AFR

AF:

0.763

Gnomad AMI

AF:

0.546

Gnomad AMR

AF:

0.715

Gnomad ASJ

AF:

0.524

Gnomad EAS

AF:

0.824

Gnomad SAS

AF:

0.685

Gnomad FIN

AF:

0.576

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.551

Gnomad OTH

AF:

0.644

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.641

AC:

97400

AN:

151904

Hom.:

31988

Cov.:

AF XY:

0.646

AC XY:

47927

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.763

AC:

31602

AN:

41426

American (AMR)

AF:

0.716

AC:

10927

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.524

AC:

1818

AN:

3470

East Asian (EAS)

AF:

0.823

AC:

4253

AN:

5166

South Asian (SAS)

AF:

0.683

AC:

3288

AN:

4814

European-Finnish (FIN)

AF:

0.576

AC:

6065

AN:

10530

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.551

AC:

37404

AN:

67916

Other (OTH)

AF:

0.648

AC:

1368

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

1753

3507

5260

7014

8767

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

786

1572

2358

3144

3930

<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.:

25428

Bravo

AF:

0.656

Asia WGS

AF:

0.775

AC:

2693

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

6.6

(source)

DANN

Benign

0.39

PhyloP100

-0.0060

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over