chr5-90694507-A-G

Variant names:

Variant summary

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

The NM_032119.4(ADGRV1):c.7751A>G(p.Asn2584Ser) variant causes a missense change. The variant allele was found at a frequency of 0.669 in 1,613,680 control chromosomes in the GnomAD database, including 366,238 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 42791 hom., cov: 32)

Exomes 𝑓: 0.66 ( 323447 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 6.65

Publications

45 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=8.266668E-7).

BP6

Variant 5-90694507-A-G is Benign according to our data. Variant chr5-90694507-A-G is described in ClinVar as Benign. ClinVar VariationId is 46379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

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.7751A>G	p.Asn2584Ser	missense	Exon 33 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.7767A>G		non_coding_transcript_exon	Exon 33 of 90

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.7751A>G	p.Asn2584Ser	missense	Exon 33 of 90	ENSP00000384582.2	Q8WXG9-1
ADGRV1	ENST00000509621.1	TSL:1	n.448A>G		non_coding_transcript_exon	Exon 1 of 26
ADGRV1	ENST00000640403.1	TSL:5	c.5042A>G	p.Asn1681Ser	missense	Exon 23 of 29	ENSP00000492531.1	A0A1W2PRC7

Frequencies

GnomAD3 genomes

AF:

0.740

AC:

112460

AN:

152022

Hom.:

42715

Cov.:

show subpopulations

Gnomad AFR

AF:

0.911

Gnomad AMI

AF:

0.714

Gnomad AMR

AF:

0.774

Gnomad ASJ

AF:

0.669

Gnomad EAS

AF:

0.812

Gnomad SAS

AF:

0.726

Gnomad FIN

AF:

0.662

Gnomad MID

AF:

0.687

Gnomad NFE

AF:

0.640

Gnomad OTH

AF:

0.744

GnomAD2 exomes

AF:

0.711

AC:

177017

AN:

249062

AF XY:

0.702

show subpopulations

Gnomad AFR exome

AF:

0.917

Gnomad AMR exome

AF:

0.826

Gnomad ASJ exome

AF:

0.666

Gnomad EAS exome

AF:

0.801

Gnomad FIN exome

AF:

0.668

Gnomad NFE exome

AF:

0.643

Gnomad OTH exome

AF:

0.701

GnomAD4 exome

AF:

0.662

AC:

967644

AN:

1461540

Hom.:

323447

Cov.:

AF XY:

0.662

AC XY:

481104

AN XY:

727064

show subpopulations

African (AFR)

AF:

0.916

AC:

30672

AN:

33468

American (AMR)

AF:

0.821

AC:

36734

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.666

AC:

17397

AN:

26134

East Asian (EAS)

AF:

0.818

AC:

32479

AN:

39696

South Asian (SAS)

AF:

0.720

AC:

62070

AN:

86256

European-Finnish (FIN)

AF:

0.667

AC:

35631

AN:

53398

Middle Eastern (MID)

AF:

0.696

AC:

4016

AN:

5768

European-Non Finnish (NFE)

AF:

0.636

AC:

707102

AN:

1111728

Other (OTH)

AF:

0.688

AC:

41543

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

20558

41116

61675

82233

102791

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18884

37768

56652

75536

94420

<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:

0.740

AC:

112590

AN:

152140

Hom.:

42791

Cov.:

AF XY:

0.742

AC XY:

55186

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.911

AC:

37832

AN:

41522

American (AMR)

AF:

0.774

AC:

11824

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.669

AC:

2321

AN:

3468

East Asian (EAS)

AF:

0.813

AC:

4210

AN:

5178

South Asian (SAS)

AF:

0.724

AC:

3495

AN:

4830

European-Finnish (FIN)

AF:

0.662

AC:

6994

AN:

10564

Middle Eastern (MID)

AF:

0.687

AC:

202

AN:

294

European-Non Finnish (NFE)

AF:

0.640

AC:

43484

AN:

67988

Other (OTH)

AF:

0.747

AC:

1577

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1436

2873

4309

5746

7182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

836

1672

2508

3344

4180

<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:

0.677

Hom.:

159551

Bravo

AF:

0.760

TwinsUK

AF:

0.630

AC:

2335

ALSPAC

AF:

0.649

AC:

2501

ESP6500AA

AF:

0.915

AC:

3558

ESP6500EA

AF:

0.645

AC:

5356

ExAC

AF:

0.709

AC:

85654

Asia WGS

AF:

0.809

AC:

2813

AN:

3478

EpiCase

AF:

0.651

EpiControl

AF:

0.649

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

not provided (2)

Usher syndrome type 2C (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.029

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.25

DEOGEN2

Benign

0.095

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.19

MetaRNN

Benign

8.3e-7

MetaSVM

Benign

-0.95

PhyloP100

6.7

PrimateAI

Benign

0.46

PROVEAN

Benign

1.7

REVEL

Benign

0.15

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.019

MPC

0.041

ClinPred

0.013

GERP RS

5.9

Varity_R

0.10

gMVP

0.16

Mutation Taster

=88/12

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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