rs371947306

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_032119.4(ADGRV1):c.16377G>T(p.Gln5459His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000403 in 1,578,762 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00027 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 6 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:6

Conservation

PhyloP100: 0.00500

Publications

4 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: Orphanet, ClinGen
Usher syndrome type 2C
Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005907178).

BP6

Variant 5-90828952-G-T is Benign according to our data. Variant chr5-90828952-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 163623.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00027 (41/152080) while in subpopulation SAS AF = 0.00747 (36/4818). AF 95% confidence interval is 0.00555. There are 1 homozygotes in GnomAd4. There are 33 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 6 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032119.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	NM_032119.4	MANE Select	c.16377G>T	p.Gln5459His	missense	Exon 77 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.16393G>T		non_coding_transcript_exon	Exon 77 of 90

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.16377G>T	p.Gln5459His	missense	Exon 77 of 90	ENSP00000384582.2	Q8WXG9-1
ADGRV1	ENST00000638510.1	TSL:1	n.3644G>T		non_coding_transcript_exon	Exon 13 of 26
ADGRV1	ENST00000425867.3	TSL:5	c.5331G>T	p.Gln1777His	missense	Exon 25 of 38	ENSP00000392618.3	A0A1X7SBU6

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

151964

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00767

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.000953

AC:

232

AN:

243394

AF XY:

0.00129

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000565

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000343

GnomAD4 exome

AF:

0.000418

AC:

596

AN:

1426682

Hom.:

Cov.:

AF XY:

0.000603

AC XY:

426

AN XY:

706998

show subpopulations

African (AFR)

AF:

0.0000303

AC:

AN:

32992

American (AMR)

AF:

0.00

AC:

AN:

43654

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25156

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39348

South Asian (SAS)

AF:

0.00726

AC:

568

AN:

78284

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51904

Middle Eastern (MID)

AF:

0.000178

AC:

AN:

5618

European-Non Finnish (NFE)

AF:

0.00000183

AC:

AN:

1090918

Other (OTH)

AF:

0.000391

AC:

AN:

58808

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

118

147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000270

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.000444

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41476

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00747

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

67978

Other (OTH)

AF:

0.000475

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000108

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.00100

AC:

121

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Usher syndrome type 2C (2)

not specified (1)

Usher syndrome type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.32

CADD

Benign

0.17

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.14

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.53

M_CAP

Benign

0.012

MetaRNN

Benign

0.0059

MetaSVM

Benign

-1.1

PhyloP100

0.0050

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.3

REVEL

Benign

0.21

Sift

Benign

0.053

Sift4G

Uncertain

0.0040

Polyphen

0.0010

Vest4

0.20

MutPred

0.60

Loss of ubiquitination at K5456 (P = 0.0755)

MVP

0.072

MPC

0.24

ClinPred

0.079

GERP RS

-3.6

Varity_R

0.047

gMVP

0.54

Mutation Taster

=78/22

polymorphism

(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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over