rs142013761

Variant names:

• chr5-90684016-C-T
• rs142013761
• NM_032119.4:c.6095C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-90684016-C-T
• chr5-90684016-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_032119.4(ADGRV1):​c.6095C>T​(p.Ala2032Val) variant causes a missense change. The variant allele was found at a frequency of 0.000542 in 1,613,824 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A2032A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0028 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00031 (2 hom.)
• Consequence: ADGRV1 NM_032119.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 4.08
• Publications: 7 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0075790286).
• BP6: Variant 5-90684016-C-T is Benign according to our data. Variant chr5-90684016-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 46347.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 = 0.00277 (422/152166) while in subpopulation AFR AF = 0.00977 (406/41536). AF 95% confidence interval is 0.00899. There are 1 homozygotes in GnomAd4. There are 208 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR,AD 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.6095C>T	p.Ala2032Val	missense	Exon 28 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.6194C>T		non_coding_transcript_exon	Exon 28 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.6095C>T	p.Ala2032Val	missense	Exon 28 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000640403.1	TSL:5	c.3386C>T	p.Ala1129Val	missense	Exon 18 of 29	ENSP00000492531.1	A0A1W2PRC7
	ADGRV1	ENST00000639473.1	TSL:5	n.1554C>T		non_coding_transcript_exon	Exon 8 of 23

Frequencies

GnomAD3 genomes AF: 0.00278 AC: 422 AN: 152046 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00980

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

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: 0.00192

GnomAD2 exomes AF: 0.000684 AC: 170 AN: 248672 AF XY: 0.000608

Gnomad AFR exome AF: 0.00995

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000533

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000309 AC: 452 AN: 1461658 Hom.: 2 Cov.: 34 AF XY: 0.000286 AC XY: 208 AN XY: 727106

African (AFR) AF: 0.0102 AC: 340 AN: 33478

American (AMR) AF: 0.000246 AC: 11 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39690

South Asian (SAS) AF: 0.0000927 AC: 8 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53390

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000558 AC: 62 AN: 1111852

Other (OTH) AF: 0.000447 AC: 27 AN: 60374

GnomAD4 genome AF: 0.00277 AC: 422 AN: 152166 Hom.: 1 Cov.: 32 AF XY: 0.00280 AC XY: 208 AN XY: 74390

African (AFR) AF: 0.00977 AC: 406 AN: 41536

American (AMR) AF: 0.000589 AC: 9 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68000

Other (OTH) AF: 0.00190 AC: 4 AN: 2106

Alfa AF: 0.000845 Hom.: 2

Bravo AF: 0.00298

ESP6500AA AF: 0.00950 AC: 35

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000820 AC: 99

Asia WGS AF: 0.00144 AC: 5 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not provided (5)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.54
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0076	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.1
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.081
Sift	Benign	0.097	T
Sift4G	Benign	0.13	T
Polyphen		0.88	P
Vest4		0.12
MVP		0.70
MPC		0.32
ClinPred		0.029	T
GERP RS		5.7
Varity_R		0.15
gMVP		0.61
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs142013761; hg19: chr5-89979833; COSMIC: COSV67984832;