5-90757026-C-T

Variant names:

• chr5-90757026-C-T
• rs144269892
• NM_032119.4:c.11805C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4 BP6_Very_Strong BP7 BS1

The NM_032119.4(ADGRV1):​c.11805C>T​(p.Asn3935Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000257 in 1,613,632 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (1 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.638
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.277).
• BP6: Variant 5-90757026-C-T is Benign according to our data. Variant chr5-90757026-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 497242.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.638 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00114 (173/152286) while in subpopulation AFR AF = 0.00378 (157/41558). AF 95% confidence interval is 0.0033. There are 0 homozygotes in GnomAd4. There are 80 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.11805C>T	p.Asn3935Asn	synonymous	Exon 57 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.11821C>T		non_coding_transcript_exon	Exon 57 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.11805C>T	p.Asn3935Asn	synonymous	Exon 57 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000509621.1	TSL:1	n.4502C>T		non_coding_transcript_exon	Exon 25 of 26
	ADGRV1	ENST00000425867.3	TSL:5	c.759C>T	p.Asn253Asn	synonymous	Exon 5 of 38	ENSP00000392618.3	A0A1X7SBU6

Frequencies

GnomAD3 genomes AF: 0.00114 AC: 174 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00381

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000402 AC: 100 AN: 248780 AF XY: 0.000274

Gnomad AFR exome AF: 0.00420

Gnomad AMR exome AF: 0.000783

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000710

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000165 AC: 241 AN: 1461346 Hom.: 1 Cov.: 31 AF XY: 0.000149 AC XY: 108 AN XY: 726938

African (AFR) AF: 0.00400 AC: 134 AN: 33474

American (AMR) AF: 0.000671 AC: 30 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5764

European-Non Finnish (NFE) AF: 0.0000351 AC: 39 AN: 1111646

Other (OTH) AF: 0.000563 AC: 34 AN: 60360

GnomAD4 genome AF: 0.00114 AC: 173 AN: 152286 Hom.: 0 Cov.: 32 AF XY: 0.00107 AC XY: 80 AN XY: 74464

African (AFR) AF: 0.00378 AC: 157 AN: 41558

American (AMR) AF: 0.000784 AC: 12 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68028

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000635 Hom.: 0

Bravo AF: 0.00139

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0000546

EpiControl AF: 0.0000594

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.0
DANN	Benign	0.36
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism

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: rs144269892; hg19: chr5-90052843; COSMIC: COSV101315938;