5-90642617-G-T

Variant names:

• chr5-90642617-G-T
• rs1344030
• NM_032119.4:c.2241-19G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032119.4(ADGRV1):​c.2241-19G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,604,350 control chromosomes in the GnomAD database, including 24,003 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2691 hom., cov: 32)
  • Exomes 𝑓: 0.16 (21312 hom.)
• Consequence: ADGRV1 NM_032119.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.615
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-90642617-G-T is Benign according to our data. Variant chr5-90642617-G-T is described in ClinVar as Benign. ClinVar VariationId is 137502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 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.2241-19G>T		intron	N/A	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.2340-19G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.2241-19G>T		intron	N/A	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000640403.1	TSL:5	c.-457-19G>T		intron	N/A	ENSP00000492531.1	A0A1W2PRC7
	ADGRV1	ENST00000504142.2	TSL:5	n.1007-19G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27498 AN: 151870 Hom.: 2679 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.175

GnomAD2 exomes AF: 0.188 AC: 45269 AN: 240940 AF XY: 0.188

Gnomad AFR exome AF: 0.201

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.222

Gnomad EAS exome AF: 0.404

Gnomad FIN exome AF: 0.191

Gnomad NFE exome AF: 0.153

Gnomad OTH exome AF: 0.175

GnomAD4 exome AF: 0.164 AC: 237845 AN: 1452362 Hom.: 21312 Cov.: 31 AF XY: 0.166 AC XY: 119757 AN XY: 721968

African (AFR) AF: 0.204 AC: 6704 AN: 32928

American (AMR) AF: 0.142 AC: 6134 AN: 43052

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 5595 AN: 25678

East Asian (EAS) AF: 0.385 AC: 15255 AN: 39620

South Asian (SAS) AF: 0.225 AC: 18790 AN: 83666

European-Finnish (FIN) AF: 0.184 AC: 9793 AN: 53194

Middle Eastern (MID) AF: 0.183 AC: 1045 AN: 5720

European-Non Finnish (NFE) AF: 0.148 AC: 163645 AN: 1108502

Other (OTH) AF: 0.181 AC: 10884 AN: 60002

GnomAD4 genome AF: 0.181 AC: 27539 AN: 151988 Hom.: 2691 Cov.: 32 AF XY: 0.185 AC XY: 13751 AN XY: 74296

African (AFR) AF: 0.201 AC: 8323 AN: 41462

American (AMR) AF: 0.150 AC: 2292 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 767 AN: 3468

East Asian (EAS) AF: 0.403 AC: 2085 AN: 5174

South Asian (SAS) AF: 0.230 AC: 1108 AN: 4818

European-Finnish (FIN) AF: 0.183 AC: 1935 AN: 10552

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10482 AN: 67940

Other (OTH) AF: 0.182 AC: 385 AN: 2114

Alfa AF: 0.157 Hom.: 3640

Bravo AF: 0.179

Asia WGS AF: 0.316 AC: 1097 AN: 3478

ClinVar

ClinVar submissions

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	-0.90
CADD	Benign	3.6
DANN	Benign	0.50
PhyloP100		0.61
Mutation Taster		=100/0	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: rs1344030; hg19: chr5-89938434; COSMIC: COSV67978715; COSMIC: COSV67978715;