rs62000408

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.14029T>C(p.Phe4677Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00699 in 1,446,920 control chromosomes in the GnomAD database, including 636 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 0.035 ( 331 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 305 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.05

Publications

5 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=0.0012586713).

BP6

Variant 5-90789837-T-C is Benign according to our data. Variant chr5-90789837-T-C is described in ClinVar as Benign. ClinVar VariationId is 46269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 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.14029T>C	p.Phe4677Leu	missense	Exon 69 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.14045T>C		non_coding_transcript_exon	Exon 69 of 90

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.14029T>C	p.Phe4677Leu	missense	Exon 69 of 90	ENSP00000384582.2	Q8WXG9-1
ADGRV1	ENST00000638510.1	TSL:1	n.1296T>C		non_coding_transcript_exon	Exon 5 of 26
ADGRV1	ENST00000425867.3	TSL:5	c.2983T>C	p.Phe995Leu	missense	Exon 17 of 38	ENSP00000392618.3	A0A1X7SBU6

Frequencies

GnomAD3 genomes

AF:

0.0350

AC:

5326

AN:

152144

Hom.:

330

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0119

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.0100

AC:

1334

AN:

132946

AF XY:

0.00781

show subpopulations

Gnomad AFR exome

AF:

0.132

Gnomad AMR exome

AF:

0.00790

Gnomad ASJ exome

AF:

0.00389

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000292

Gnomad OTH exome

AF:

0.00491

GnomAD4 exome

AF:

0.00368

AC:

4764

AN:

1294658

Hom.:

305

Cov.:

AF XY:

0.00334

AC XY:

2108

AN XY:

631158

show subpopulations

African (AFR)

AF:

0.132

AC:

3833

AN:

28978

American (AMR)

AF:

0.00815

AC:

195

AN:

23922

Ashkenazi Jewish (ASJ)

AF:

0.00394

AC:

AN:

21566

East Asian (EAS)

AF:

0.00

AC:

AN:

35736

South Asian (SAS)

AF:

0.000346

AC:

AN:

57780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46048

Middle Eastern (MID)

AF:

0.00480

AC:

AN:

5210

European-Non Finnish (NFE)

AF:

0.000138

AC:

141

AN:

1022718

Other (OTH)

AF:

0.00882

AC:

465

AN:

52700

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

187

374

562

749

936

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

264

396

528

660

<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:

0.0351

AC:

5343

AN:

152262

Hom.:

331

Cov.:

AF XY:

0.0338

AC XY:

2516

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.122

AC:

5084

AN:

41528

American (AMR)

AF:

0.0118

AC:

181

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00375

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000621

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000441

AC:

AN:

68014

Other (OTH)

AF:

0.0151

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

226

453

679

906

1132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0120

Hom.:

208

Bravo

AF:

0.0405

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.111

AC:

398

ESP6500EA

AF:

0.000246

AC:

ExAC

AF:

0.00873

AC:

999

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.37

DEOGEN2

Benign

0.078

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0013

MetaSVM

Benign

-0.98

PhyloP100

1.1

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.29

REVEL

Benign

0.049

Sift

Benign

0.51

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.039

MutPred

0.38

Loss of methylation at K4674 (P = 0.1816)

MPC

0.071

ClinPred

0.0042

GERP RS

-0.57

Varity_R

0.056

gMVP

0.35

Mutation Taster

=91/9

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