rs200392821

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_032119.4(ADGRV1):c.5282C>G(p.Ser1761Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000119 in 1,613,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S1761S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00063 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:4

Conservation

PhyloP100: 7.67

Publications

2 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: Labcorp Genetics (formerly Invitae), G2P
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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012378126).

BP6

Variant 5-90675414-C-G is Benign according to our data. Variant chr5-90675414-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 163574.

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.5282C>G	p.Ser1761Cys	missense	Exon 24 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.5381C>G		non_coding_transcript_exon	Exon 24 of 90

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.5282C>G	p.Ser1761Cys	missense	Exon 24 of 90	ENSP00000384582.2	Q8WXG9-1
ADGRV1	ENST00000450321.2	TSL:1	n.*400C>G		non_coding_transcript_exon	Exon 4 of 6	ENSP00000492054.1	A0A1W2PR51
ADGRV1	ENST00000450321.2	TSL:1	n.*400C>G		3_prime_UTR	Exon 4 of 6	ENSP00000492054.1	A0A1W2PR51

Frequencies

GnomAD3 genomes

AF:

0.000631

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000177

AC:

AN:

248602

AF XY:

0.000126

show subpopulations

Gnomad AFR exome

AF:

0.00278

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000657

AC:

AN:

1461390

Hom.:

Cov.:

AF XY:

0.0000660

AC XY:

AN XY:

726940

show subpopulations

African (AFR)

AF:

0.00260

AC:

AN:

33476

American (AMR)

AF:

0.0000448

AC:

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86166

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111754

Other (OTH)

AF:

0.0000994

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.000631

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.000739

AC XY:

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.00226

AC:

AN:

41538

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000113

Hom.:

Bravo

AF:

0.000616

ESP6500AA

AF:

0.00228

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000232

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

ADGRV1-related disorder (1)

not specified (1)

Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.78

M_CAP

Benign

0.064

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.68

PhyloP100

7.7

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.23

Sift

Uncertain

0.012

Sift4G

Benign

0.075

Polyphen

0.99

Vest4

0.44

MVP

0.74

MPC

0.28

ClinPred

0.16

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.23

gMVP

0.41

Mutation Taster

=68/32

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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