chr5-90755077-G-A

Variant names:

• chr5-90755077-G-A
• rs74327115
• NM_032119.4:c.11472G>A

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.11472G>A​(p.Leu3824Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0044 in 1,610,576 control chromosomes in the GnomAD database, including 276 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. L3824L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.023 (155 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (121 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.0590
• 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: ClinGen, Orphanet
• Usher syndrome type 2C

  Inheritance: AR Classification: STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• 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=0.035).
• BP6: Variant 5-90755077-G-A is Benign according to our data. Variant chr5-90755077-G-A is described in ClinVar as Benign. ClinVar VariationId is 46255.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.059 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0792 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	NM_032119.4	MANE Select	c.11472G>A	p.Leu3824Leu	synonymous	Exon 55 of 90	NP_115495.3
	ADGRV1	NR_003149.2		n.11488G>A		non_coding_transcript_exon	Exon 55 of 90

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.11472G>A	p.Leu3824Leu	synonymous	Exon 55 of 90	ENSP00000384582.2
	ADGRV1	ENST00000509621.1	TSL:1	n.4169G>A		non_coding_transcript_exon	Exon 23 of 26
	ADGRV1	ENST00000425867.3	TSL:5	c.603G>A	p.Leu201Leu	synonymous	Exon 4 of 38	ENSP00000392618.3

Frequencies

GnomAD3 genomes AF: 0.0233 AC: 3545 AN: 152082 Hom.: 154 Cov.: 32

Gnomad AFR AF: 0.0815

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00676

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00617 AC: 1535 AN: 248958 AF XY: 0.00462

Gnomad AFR exome AF: 0.0861

Gnomad AMR exome AF: 0.00371

Gnomad ASJ exome AF: 0.00348

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000142

Gnomad OTH exome AF: 0.00314

GnomAD4 exome AF: 0.00243 AC: 3539 AN: 1458376 Hom.: 121 Cov.: 29 AF XY: 0.00215 AC XY: 1560 AN XY: 725738

African (AFR) AF: 0.0832 AC: 2779 AN: 33396

American (AMR) AF: 0.00400 AC: 179 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00387 AC: 101 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53338

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5762

European-Non Finnish (NFE) AF: 0.000118 AC: 131 AN: 1108958

Other (OTH) AF: 0.00529 AC: 319 AN: 60248

GnomAD4 genome AF: 0.0233 AC: 3551 AN: 152200 Hom.: 155 Cov.: 32 AF XY: 0.0221 AC XY: 1643 AN XY: 74428

African (AFR) AF: 0.0815 AC: 3385 AN: 41538

American (AMR) AF: 0.00662 AC: 101 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 68014

Other (OTH) AF: 0.0114 AC: 24 AN: 2108

Alfa AF: 0.00852 Hom.: 29

Bravo AF: 0.0261

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000296

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	-0.45
CADD	Benign	4.4
DANN	Benign	0.81
PhyloP100		-0.059
Mutation Taster		=97/3	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: rs74327115; hg19: chr5-90050894; COSMIC: COSV67991693; COSMIC: COSV67991693;