5-90658032-C-T

Variant names:

• chr5-90658032-C-T
• rs17543819
• NM_032119.4:c.4506C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_032119.4(ADGRV1):​c.4506C>T​(p.Pro1502Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0725 in 1,613,504 control chromosomes in the GnomAD database, including 4,803 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P1502P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.059 (350 hom., cov: 32)
  • Exomes 𝑓: 0.074 (4453 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7 O:1
• Conservation: PhyloP100: -1.04
• Publications: 16 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 5-90658032-C-T is Benign according to our data. Variant chr5-90658032-C-T is described in ClinVar as Benign. ClinVar VariationId is 46329.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.04 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.104 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.4506C>T	p.Pro1502Pro	synonymous	Exon 21 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.4605C>T		non_coding_transcript_exon	Exon 21 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.4506C>T	p.Pro1502Pro	synonymous	Exon 21 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000640403.1	TSL:5	c.1797C>T	p.Pro599Pro	synonymous	Exon 11 of 29	ENSP00000492531.1	A0A1W2PRC7
	ADGRV1	ENST00000639676.1	TSL:5	n.2104C>T		non_coding_transcript_exon	Exon 9 of 11

Frequencies

GnomAD3 genomes AF: 0.0593 AC: 9011 AN: 151890 Hom.: 352 Cov.: 32

Gnomad AFR AF: 0.0254

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.0602

Gnomad ASJ AF: 0.0851

Gnomad EAS AF: 0.00559

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0488

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0802

Gnomad OTH AF: 0.0605

GnomAD2 exomes AF: 0.0674 AC: 16783 AN: 249156 AF XY: 0.0719

Gnomad AFR exome AF: 0.0246

Gnomad AMR exome AF: 0.0427

Gnomad ASJ exome AF: 0.0859

Gnomad EAS exome AF: 0.00484

Gnomad FIN exome AF: 0.0462

Gnomad NFE exome AF: 0.0814

Gnomad OTH exome AF: 0.0717

GnomAD4 exome AF: 0.0739 AC: 107978 AN: 1461496 Hom.: 4453 Cov.: 32 AF XY: 0.0756 AC XY: 54937 AN XY: 727018

African (AFR) AF: 0.0223 AC: 748 AN: 33480

American (AMR) AF: 0.0449 AC: 2007 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0857 AC: 2239 AN: 26122

East Asian (EAS) AF: 0.00292 AC: 116 AN: 39692

South Asian (SAS) AF: 0.109 AC: 9432 AN: 86190

European-Finnish (FIN) AF: 0.0516 AC: 2753 AN: 53398

Middle Eastern (MID) AF: 0.104 AC: 598 AN: 5768

European-Non Finnish (NFE) AF: 0.0770 AC: 85653 AN: 1111762

Other (OTH) AF: 0.0734 AC: 4432 AN: 60366

GnomAD4 genome AF: 0.0592 AC: 9002 AN: 152008 Hom.: 350 Cov.: 32 AF XY: 0.0589 AC XY: 4379 AN XY: 74304

African (AFR) AF: 0.0254 AC: 1055 AN: 41480

American (AMR) AF: 0.0602 AC: 919 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0851 AC: 295 AN: 3468

East Asian (EAS) AF: 0.00561 AC: 29 AN: 5172

South Asian (SAS) AF: 0.112 AC: 539 AN: 4802

European-Finnish (FIN) AF: 0.0488 AC: 515 AN: 10550

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0802 AC: 5450 AN: 67950

Other (OTH) AF: 0.0594 AC: 125 AN: 2106

Alfa AF: 0.0743 Hom.: 580

Bravo AF: 0.0556

EpiCase AF: 0.0867

EpiControl AF: 0.0883

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (3)
-	-	1	Febrile seizures, familial, 4;C2931213:Usher syndrome type 2C (1)
-	-	1	Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.7
DANN	Benign	0.74
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs17543819; hg19: chr5-89953849; COSMIC: COSV67985294; COSMIC: COSV67985294;