rs35791889

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.5747C>T(p.Thr1916Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00195 in 1,613,762 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T1916T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.011 ( 29 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 28 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.93

Publications

13 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055490136).

BP6

Variant 5-90683668-C-T is Benign according to our data. Variant chr5-90683668-C-T is described in ClinVar as Benign. ClinVar VariationId is 158653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0105 (1599/152216) while in subpopulation AFR AF = 0.0365 (1517/41528). AF 95% confidence interval is 0.035. There are 29 homozygotes in GnomAd4. There are 746 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 29 AD,AR 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.5747C>T	p.Thr1916Ile	missense	Exon 28 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.5846C>T		non_coding_transcript_exon	Exon 28 of 90

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.5747C>T	p.Thr1916Ile	missense	Exon 28 of 90	ENSP00000384582.2	Q8WXG9-1
ADGRV1	ENST00000640403.1	TSL:5	c.3038C>T	p.Thr1013Ile	missense	Exon 18 of 29	ENSP00000492531.1	A0A1W2PRC7
ADGRV1	ENST00000639473.1	TSL:5	n.1206C>T		non_coding_transcript_exon	Exon 8 of 23

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

1588

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0364

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00413

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:

0.0000441

Gnomad OTH

AF:

0.00766

GnomAD2 exomes

AF:

0.00274

AC:

683

AN:

248820

AF XY:

0.00215

show subpopulations

Gnomad AFR exome

AF:

0.0396

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.000829

GnomAD4 exome

AF:

0.00106

AC:

1554

AN:

1461546

Hom.:

Cov.:

AF XY:

0.000930

AC XY:

676

AN XY:

727040

show subpopulations

African (AFR)

AF:

0.0370

AC:

1239

AN:

33472

American (AMR)

AF:

0.00172

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.000174

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.00277

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000405

AC:

AN:

1111776

Other (OTH)

AF:

0.00267

AC:

161

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

Heterozygous variant carriers

173

260

346

433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.0105

AC:

1599

AN:

152216

Hom.:

Cov.:

AF XY:

0.0100

AC XY:

746

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0365

AC:

1517

AN:

41528

American (AMR)

AF:

0.00412

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68012

Other (OTH)

AF:

0.00758

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

147

221

294

368

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:

0.00352

Hom.:

Bravo

AF:

0.0119

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0382

AC:

149

ESP6500EA

AF:

0.000363

AC:

ExAC

AF:

0.00346

AC:

418

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (2)

Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.69

MetaRNN

Benign

0.0055

MetaSVM

Benign

-1.1

PhyloP100

2.9

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.11

Sift

Uncertain

0.015

Sift4G

Benign

0.067

Polyphen

1.0

Vest4

0.27

MVP

0.74

MPC

0.32

ClinPred

0.021

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.36

gMVP

0.48

Mutation Taster

=80/20

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

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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