5-90756555-C-T

Variant names:

• chr5-90756555-C-T
• rs2438349
• NM_032119.4:c.11682C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_032119.4(ADGRV1):​c.11682C>T​(p.Pro3894Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 1,610,038 control chromosomes in the GnomAD database, including 178,559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (21400 hom., cov: 31)
  • Exomes 𝑓: 0.46 (157159 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.842
• Publications: 25 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.147).
• BP6: Variant 5-90756555-C-T is Benign according to our data. Variant chr5-90756555-C-T is described in ClinVar as Benign. ClinVar VariationId is 46258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.842 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 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.11682C>T	p.Pro3894Pro	synonymous	Exon 56 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.11698C>T		non_coding_transcript_exon	Exon 56 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.11682C>T	p.Pro3894Pro	synonymous	Exon 56 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000509621.1	TSL:1	n.4379C>T		non_coding_transcript_exon	Exon 24 of 26
	ADGRV1	ENST00000425867.3	TSL:5	c.712-424C>T		intron	N/A	ENSP00000392618.3	A0A1X7SBU6

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78972 AN: 151736 Hom.: 21360 Cov.: 31

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.519

GnomAD2 exomes AF: 0.487 AC: 121081 AN: 248730 AF XY: 0.474

Gnomad AFR exome AF: 0.676

Gnomad AMR exome AF: 0.675

Gnomad ASJ exome AF: 0.371

Gnomad EAS exome AF: 0.456

Gnomad FIN exome AF: 0.443

Gnomad NFE exome AF: 0.446

Gnomad OTH exome AF: 0.486

GnomAD4 exome AF: 0.460 AC: 670601 AN: 1458184 Hom.: 157159 Cov.: 34 AF XY: 0.456 AC XY: 330690 AN XY: 725490

African (AFR) AF: 0.672 AC: 22459 AN: 33416

American (AMR) AF: 0.666 AC: 29736 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 9880 AN: 26118

East Asian (EAS) AF: 0.504 AC: 19986 AN: 39638

South Asian (SAS) AF: 0.420 AC: 36112 AN: 86078

European-Finnish (FIN) AF: 0.448 AC: 23885 AN: 53358

Middle Eastern (MID) AF: 0.456 AC: 2625 AN: 5758

European-Non Finnish (NFE) AF: 0.449 AC: 497724 AN: 1108898

Other (OTH) AF: 0.468 AC: 28194 AN: 60242

GnomAD4 genome AF: 0.521 AC: 79070 AN: 151854 Hom.: 21400 Cov.: 31 AF XY: 0.521 AC XY: 38671 AN XY: 74188

African (AFR) AF: 0.668 AC: 27652 AN: 41418

American (AMR) AF: 0.598 AC: 9135 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1314 AN: 3462

East Asian (EAS) AF: 0.483 AC: 2487 AN: 5154

South Asian (SAS) AF: 0.416 AC: 1999 AN: 4800

European-Finnish (FIN) AF: 0.448 AC: 4704 AN: 10500

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.444 AC: 30134 AN: 67938

Other (OTH) AF: 0.515 AC: 1086 AN: 2110

Alfa AF: 0.470 Hom.: 9394

Bravo AF: 0.543

Asia WGS AF: 0.477 AC: 1659 AN: 3478

EpiCase AF: 0.447

EpiControl AF: 0.446

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	not provided (3)
-	-	1	Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	1.8
DANN	Benign	0.24
PhyloP100		0.84
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2438349; hg19: chr5-90052372; COSMIC: COSV67980909; COSMIC: COSV67980909;