rs138929990

Variant names:

• chr5-90653723-C-T
• rs138929990
• NM_032119.4:c.4149C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-90653723-C-T
• chr5-90653723-C-G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_032119.4(ADGRV1):​c.4149C>T​(p.Tyr1383Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,612,810 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0410
• Publications: 0 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.133).
• BP6: Variant 5-90653723-C-T is Benign according to our data. Variant chr5-90653723-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 178360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.041 with no splicing effect.

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.4149C>T	p.Tyr1383Tyr	synonymous	Exon 20 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.4248C>T		non_coding_transcript_exon	Exon 20 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.4149C>T	p.Tyr1383Tyr	synonymous	Exon 20 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000640403.1	TSL:5	c.1440C>T	p.Tyr480Tyr	synonymous	Exon 10 of 29	ENSP00000492531.1	A0A1W2PRC7
	ADGRV1	ENST00000504142.2	TSL:5	n.2915C>T		non_coding_transcript_exon	Exon 14 of 14

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152106 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000366 AC: 9 AN: 246212 AF XY: 0.0000450

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000293

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000561

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000539

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.0000260 AC: 38 AN: 1460586 Hom.: 0 Cov.: 32 AF XY: 0.0000220 AC XY: 16 AN XY: 726428

African (AFR) AF: 0.0000299 AC: 1 AN: 33472

American (AMR) AF: 0.0000225 AC: 1 AN: 44518

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39674

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000252 AC: 28 AN: 1111364

Other (OTH) AF: 0.0000497 AC: 3 AN: 60348

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152224 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74416

African (AFR) AF: 0.00 AC: 0 AN: 41534

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000416

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	ADGRV1-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	2.2
DANN	Benign	0.18
PhyloP100		-0.041

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: rs138929990; hg19: chr5-89949540; COSMIC: COSV101316752; COSMIC: COSV101316752;