rs17544552

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000405460.9(ADGRV1):c.5780C>T(p.Thr1927Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0749 in 1,613,630 control chromosomes in the GnomAD database, including 5,014 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T1927T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.069 ( 418 hom., cov: 32)

Exomes 𝑓: 0.075 ( 4596 hom. )

Consequence

ADGRV1
ENST00000405460.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: -1.32

Publications

20 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014486611).

BP6

Variant 5-90683701-C-T is Benign according to our data. Variant chr5-90683701-C-T is described in ClinVar as Benign. ClinVar VariationId is 46339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000405460.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	NM_032119.4	MANE Select	c.5780C>T	p.Thr1927Met	missense	Exon 28 of 90	NP_115495.3
	ADGRV1	NR_003149.2		n.5879C>T		non_coding_transcript_exon	Exon 28 of 90

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.5780C>T	p.Thr1927Met	missense	Exon 28 of 90	ENSP00000384582.2
ADGRV1	ENST00000640403.1	TSL:5	c.3071C>T	p.Thr1024Met	missense	Exon 18 of 29	ENSP00000492531.1
ADGRV1	ENST00000639473.1	TSL:5	n.1239C>T		non_coding_transcript_exon	Exon 8 of 23

Frequencies

GnomAD3 genomes

AF:

0.0693

AC:

10530

AN:

152030

Hom.:

419

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0592

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0608

Gnomad ASJ

AF:

0.0807

Gnomad EAS

AF:

0.0179

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.0487

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0798

Gnomad OTH

AF:

0.0708

GnomAD2 exomes

AF:

0.0717

AC:

17827

AN:

248806

AF XY:

0.0760

show subpopulations

Gnomad AFR exome

AF:

0.0624

Gnomad AMR exome

AF:

0.0441

Gnomad ASJ exome

AF:

0.0823

Gnomad EAS exome

AF:

0.0178

Gnomad FIN exome

AF:

0.0460

Gnomad NFE exome

AF:

0.0804

Gnomad OTH exome

AF:

0.0753

GnomAD4 exome

AF:

0.0755

AC:

110293

AN:

1461482

Hom.:

4596

Cov.:

AF XY:

0.0773

AC XY:

56226

AN XY:

726992

show subpopulations

African (AFR)

AF:

0.0571

AC:

1911

AN:

33480

American (AMR)

AF:

0.0464

AC:

2075

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.0822

AC:

2148

AN:

26136

East Asian (EAS)

AF:

0.00993

AC:

394

AN:

39690

South Asian (SAS)

AF:

0.120

AC:

10354

AN:

86250

European-Finnish (FIN)

AF:

0.0513

AC:

2737

AN:

53392

Middle Eastern (MID)

AF:

0.108

AC:

622

AN:

5768

European-Non Finnish (NFE)

AF:

0.0768

AC:

85335

AN:

1111698

Other (OTH)

AF:

0.0781

AC:

4717

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

5492

10984

16475

21967

27459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3104

6208

9312

12416

15520

<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:

0.0692

AC:

10533

AN:

152148

Hom.:

418

Cov.:

AF XY:

0.0687

AC XY:

5110

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0594

AC:

2464

AN:

41496

American (AMR)

AF:

0.0607

AC:

927

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0807

AC:

280

AN:

3470

East Asian (EAS)

AF:

0.0178

AC:

AN:

5172

South Asian (SAS)

AF:

0.125

AC:

603

AN:

4822

European-Finnish (FIN)

AF:

0.0487

AC:

516

AN:

10592

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0798

AC:

5429

AN:

68002

Other (OTH)

AF:

0.0696

AC:

147

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

501

1003

1504

2006

2507

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

256

384

512

640

<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:

0.0769

Hom.:

2098

Bravo

AF:

0.0663

TwinsUK

AF:

0.0852

AC:

316

ALSPAC

AF:

0.0786

AC:

303

ESP6500AA

AF:

0.0600

AC:

234

ESP6500EA

AF:

0.0792

AC:

655

ExAC

AF:

0.0738

AC:

8916

Asia WGS

AF:

0.0620

AC:

214

AN:

3478

EpiCase

AF:

0.0862

EpiControl

AF:

0.0873

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

not provided (2)

Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.5

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.10

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.0

PhyloP100

-1.3

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.1

REVEL

Benign

0.032

Sift

Benign

0.12

Sift4G

Benign

0.14

Polyphen

0.098

Vest4

0.021

MPC

0.081

ClinPred

0.016

GERP RS

-11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.026

gMVP

0.47

Mutation Taster

=92/8

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over