5-90693932-C-T

Variant names:

• chr5-90693932-C-T
• rs111033452
• NM_032119.4:c.7176C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_032119.4(ADGRV1):​c.7176C>T​(p.Ser2392Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00382 in 1,595,086 control chromosomes in the GnomAD database, including 18 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. S2392S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0030 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (17 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -1.74
• Publications: 4 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=-0.65).
• BP6: Variant 5-90693932-C-T is Benign according to our data. Variant chr5-90693932-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 46363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.74 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00302 (459/152230) while in subpopulation NFE AF = 0.0045 (306/68020). AF 95% confidence interval is 0.00408. There are 1 homozygotes in GnomAd4. There are 201 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 17 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.7176C>T	p.Ser2392Ser	synonymous	Exon 33 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.7192C>T		non_coding_transcript_exon	Exon 33 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.7176C>T	p.Ser2392Ser	synonymous	Exon 33 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000640403.1	TSL:5	c.4467C>T	p.Ser1489Ser	synonymous	Exon 23 of 29	ENSP00000492531.1	A0A1W2PRC7
	ADGRV1	ENST00000639473.1	TSL:5	n.2635C>T		non_coding_transcript_exon	Exon 13 of 23

Frequencies

GnomAD3 genomes AF: 0.00302 AC: 459 AN: 152112 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00450

Gnomad OTH AF: 0.00765

GnomAD2 exomes AF: 0.00347 AC: 828 AN: 238656 AF XY: 0.00372

Gnomad AFR exome AF: 0.000784

Gnomad AMR exome AF: 0.00276

Gnomad ASJ exome AF: 0.0116

Gnomad EAS exome AF: 0.0000561

Gnomad FIN exome AF: 0.000918

Gnomad NFE exome AF: 0.00507

Gnomad OTH exome AF: 0.00524

GnomAD4 exome AF: 0.00391 AC: 5639 AN: 1442856 Hom.: 17 Cov.: 30 AF XY: 0.00391 AC XY: 2795 AN XY: 714880

African (AFR) AF: 0.000545 AC: 18 AN: 33030

American (AMR) AF: 0.00248 AC: 108 AN: 43534

Ashkenazi Jewish (ASJ) AF: 0.0100 AC: 251 AN: 25098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39362

South Asian (SAS) AF: 0.000976 AC: 82 AN: 83978

European-Finnish (FIN) AF: 0.000645 AC: 34 AN: 52744

Middle Eastern (MID) AF: 0.0103 AC: 58 AN: 5632

European-Non Finnish (NFE) AF: 0.00436 AC: 4801 AN: 1100018

Other (OTH) AF: 0.00483 AC: 287 AN: 59460

GnomAD4 genome AF: 0.00302 AC: 459 AN: 152230 Hom.: 1 Cov.: 32 AF XY: 0.00270 AC XY: 201 AN XY: 74424

African (AFR) AF: 0.00108 AC: 45 AN: 41536

American (AMR) AF: 0.00308 AC: 47 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.000754 AC: 8 AN: 10606

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00450 AC: 306 AN: 68020

Other (OTH) AF: 0.00757 AC: 16 AN: 2114

Alfa AF: 0.00371 Hom.: 1

Bravo AF: 0.00327

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not provided (5)
-	-	4	not specified (4)
-	-	1	Inborn genetic diseases (1)
-	-	1	Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	3.1
DANN	Benign	0.62
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs111033452; hg19: chr5-89989749; COSMIC: COSV67981222; COSMIC: COSV67981222;