chr5-90712298-T-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBP6

The ENST00000405460.9(ADGRV1):c.9054T>G(p.Phe3018Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000561 in 1,533,716 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). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

ADGRV1
ENST00000405460.9 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 2.65

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: 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: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.22689438).

BP6

Variant 5-90712298-T-G is Benign according to our data. Variant chr5-90712298-T-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 517600.

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.9054T>G	p.Phe3018Leu	missense	Exon 42 of 90	NP_115495.3
	ADGRV1	NR_003149.2		n.9070T>G		non_coding_transcript_exon	Exon 42 of 90

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.9054T>G	p.Phe3018Leu	missense	Exon 42 of 90	ENSP00000384582.2
ADGRV1	ENST00000509621.1	TSL:1	n.1751T>G		non_coding_transcript_exon	Exon 10 of 26
ADGRV1	ENST00000639473.1	TSL:5	n.4513T>G		non_coding_transcript_exon	Exon 22 of 23

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD2 exomes

AF:

0.0000936

AC:

AN:

160290

AF XY:

0.000106

show subpopulations

Gnomad AFR exome

AF:

0.00119

Gnomad AMR exome

AF:

0.000127

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:

0.0000420

AC:

AN:

1381380

Hom.:

Cov.:

AF XY:

0.0000367

AC XY:

AN XY:

682042

show subpopulations

African (AFR)

AF:

0.00139

AC:

AN:

30966

American (AMR)

AF:

0.0000873

AC:

AN:

34352

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24918

East Asian (EAS)

AF:

0.00

AC:

AN:

36506

South Asian (SAS)

AF:

0.0000262

AC:

AN:

76440

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49444

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4826

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1066730

Other (OTH)

AF:

0.000175

AC:

AN:

57198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

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:

0.000184

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.000673

AC:

AN:

41580

American (AMR)

AF:

0.00

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.0000630

Hom.:

Bravo

AF:

0.000204

ESP6500AA

AF:

0.000280

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000176

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Uncertain

0.12

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.70

M_CAP

Benign

0.083

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.47

PhyloP100

2.7

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.7

REVEL

Uncertain

0.51

Sift

Benign

0.041

Sift4G

Pathogenic

0.0

Polyphen

0.54

Vest4

0.94

MutPred

0.87

Loss of catalytic residue at D3020 (P = 0.2991)

MVP

0.75

MPC

0.066

ClinPred

0.13

GERP RS

3.4

Varity_R

0.44

gMVP

0.75

Mutation Taster

=65/35

polymorphism

(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

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over