5-90823476-C-T

Variant names:

• chr5-90823476-C-T
• rs3763073
• NM_032119.4:c.16248C>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.16248C>T​(p.Val5416Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0278 in 1,613,782 control chromosomes in the GnomAD database, including 2,912 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. V5416V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.027 (280 hom., cov: 32)
  • Exomes 𝑓: 0.028 (2632 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.723
• 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=-0.77).
• BP6: Variant 5-90823476-C-T is Benign according to our data. Variant chr5-90823476-C-T is described in ClinVar as Benign. ClinVar VariationId is 46284.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.723 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 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.16248C>T	p.Val5416Val	synonymous	Exon 76 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.16264C>T		non_coding_transcript_exon	Exon 76 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.16248C>T	p.Val5416Val	synonymous	Exon 76 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000638510.1	TSL:1	n.3515C>T		non_coding_transcript_exon	Exon 12 of 26
	ADGRV1	ENST00000425867.3	TSL:5	c.5202C>T	p.Val1734Val	synonymous	Exon 24 of 38	ENSP00000392618.3	A0A1X7SBU6

Frequencies

GnomAD3 genomes AF: 0.0273 AC: 4158 AN: 152132 Hom.: 282 Cov.: 32

Gnomad AFR AF: 0.00345

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0242

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0412

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0147

Gnomad OTH AF: 0.0306

GnomAD2 exomes AF: 0.0500 AC: 12461 AN: 249090 AF XY: 0.0523

Gnomad AFR exome AF: 0.00349

Gnomad AMR exome AF: 0.0186

Gnomad ASJ exome AF: 0.0208

Gnomad EAS exome AF: 0.289

Gnomad FIN exome AF: 0.0465

Gnomad NFE exome AF: 0.0146

Gnomad OTH exome AF: 0.0342

GnomAD4 exome AF: 0.0279 AC: 40754 AN: 1461532 Hom.: 2632 Cov.: 30 AF XY: 0.0306 AC XY: 22270 AN XY: 727030

African (AFR) AF: 0.00355 AC: 119 AN: 33476

American (AMR) AF: 0.0181 AC: 810 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0210 AC: 549 AN: 26130

East Asian (EAS) AF: 0.291 AC: 11547 AN: 39672

South Asian (SAS) AF: 0.115 AC: 9931 AN: 86200

European-Finnish (FIN) AF: 0.0468 AC: 2500 AN: 53402

Middle Eastern (MID) AF: 0.0337 AC: 194 AN: 5764

European-Non Finnish (NFE) AF: 0.0114 AC: 12728 AN: 1111802

Other (OTH) AF: 0.0394 AC: 2376 AN: 60368

GnomAD4 genome AF: 0.0273 AC: 4149 AN: 152250 Hom.: 280 Cov.: 32 AF XY: 0.0313 AC XY: 2328 AN XY: 74450

African (AFR) AF: 0.00347 AC: 144 AN: 41554

American (AMR) AF: 0.0241 AC: 368 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3468

East Asian (EAS) AF: 0.278 AC: 1439 AN: 5168

South Asian (SAS) AF: 0.129 AC: 620 AN: 4822

European-Finnish (FIN) AF: 0.0412 AC: 437 AN: 10604

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0147 AC: 1001 AN: 68028

Other (OTH) AF: 0.0308 AC: 65 AN: 2112

Alfa AF: 0.0190 Hom.: 343

Bravo AF: 0.0237

Asia WGS AF: 0.174 AC: 604 AN: 3478

EpiCase AF: 0.0155

EpiControl AF: 0.0130

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.12
DANN	Benign	0.31
PhyloP100		-0.72
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: rs3763073; hg19: chr5-90119293; COSMIC: COSV67980983;