rs35092519

Variant names:

• chr5-90778942-G-A
• rs35092519
• NM_032119.4:c.12927G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-90778942-G-A
• chr5-90778942-G-C
• chr5-90778942-G-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.12927G>A​(p.Ala4309Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.025 in 1,613,416 control chromosomes in the GnomAD database, including 690 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. A4309A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.035 (123 hom., cov: 32)
  • Exomes 𝑓: 0.024 (567 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -2.17
• Publications: 2 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: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
• 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=-0.76).
• BP6: Variant 5-90778942-G-A is Benign according to our data. Variant chr5-90778942-G-A is described in ClinVar as Benign. ClinVar VariationId is 46264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.17 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0638 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.12927G>A	p.Ala4309Ala	synonymous	Exon 64 of 90	NP_115495.3
	ADGRV1	NR_003149.2		n.12943G>A		non_coding_transcript_exon	Exon 64 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.12927G>A	p.Ala4309Ala	synonymous	Exon 64 of 90	ENSP00000384582.2
	ADGRV1	ENST00000425867.3	TSL:5	c.1881G>A	p.Ala627Ala	synonymous	Exon 12 of 38	ENSP00000392618.3
	ADGRV1	ENST00000640464.1	TSL:5	n.3346G>A		non_coding_transcript_exon	Exon 21 of 21

Frequencies

GnomAD3 genomes AF: 0.0351 AC: 5343 AN: 152078 Hom.: 124 Cov.: 32

Gnomad AFR AF: 0.0658

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0264

Gnomad ASJ AF: 0.0827

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.0183

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0238

Gnomad OTH AF: 0.0379

GnomAD2 exomes AF: 0.0239 AC: 5948 AN: 248854 AF XY: 0.0231

Gnomad AFR exome AF: 0.0650

Gnomad AMR exome AF: 0.0156

Gnomad ASJ exome AF: 0.0771

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0193

Gnomad NFE exome AF: 0.0253

Gnomad OTH exome AF: 0.0257

GnomAD4 exome AF: 0.0239 AC: 34922 AN: 1461220 Hom.: 567 Cov.: 31 AF XY: 0.0235 AC XY: 17106 AN XY: 726902

African (AFR) AF: 0.0652 AC: 2182 AN: 33442

American (AMR) AF: 0.0183 AC: 817 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.0765 AC: 1997 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00628 AC: 542 AN: 86244

European-Finnish (FIN) AF: 0.0182 AC: 974 AN: 53402

Middle Eastern (MID) AF: 0.0340 AC: 196 AN: 5760

European-Non Finnish (NFE) AF: 0.0238 AC: 26493 AN: 1111516

Other (OTH) AF: 0.0285 AC: 1721 AN: 60342

GnomAD4 genome AF: 0.0352 AC: 5351 AN: 152196 Hom.: 123 Cov.: 32 AF XY: 0.0341 AC XY: 2535 AN XY: 74426

African (AFR) AF: 0.0658 AC: 2734 AN: 41530

American (AMR) AF: 0.0263 AC: 402 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0827 AC: 287 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.00581 AC: 28 AN: 4820

European-Finnish (FIN) AF: 0.0183 AC: 194 AN: 10612

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0238 AC: 1616 AN: 68000

Other (OTH) AF: 0.0375 AC: 79 AN: 2108

Alfa AF: 0.0293 Hom.: 48

Bravo AF: 0.0392

Asia WGS AF: 0.00779 AC: 27 AN: 3478

EpiCase AF: 0.0305

EpiControl AF: 0.0307

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.046
DANN	Benign	0.56
PhyloP100		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	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: rs35092519; hg19: chr5-90074759; COSMIC: COSV67996341; COSMIC: COSV67996341;