5-90863868-G-A

Variant names:

• chr5-90863868-G-A
• rs187039736
• NM_032119.4:c.17856+11G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_032119.4(ADGRV1):​c.17856+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00319 in 1,552,176 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (25 hom.)
• Consequence: ADGRV1 NM_032119.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -2.50
• Publications: 0 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=-1.01).
• BP6: Variant 5-90863868-G-A is Benign according to our data. Variant chr5-90863868-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 46294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00257 (391/152230) while in subpopulation NFE AF = 0.00369 (251/68006). AF 95% confidence interval is 0.00332. There are 0 homozygotes in GnomAd4. There are 168 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 25 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.17856+11G>A		intron	N/A	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.17872+11G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.17856+11G>A		intron	N/A	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000638510.1	TSL:1	n.5123+11G>A		intron	N/A
	ADGRV1	ENST00000425867.3	TSL:5	c.6810+11G>A		intron	N/A	ENSP00000392618.3	A0A1X7SBU6

Frequencies

GnomAD3 genomes AF: 0.00257 AC: 391 AN: 152112 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000893

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00369

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00275 AC: 678 AN: 246768 AF XY: 0.00265

Gnomad AFR exome AF: 0.000583

Gnomad AMR exome AF: 0.000792

Gnomad ASJ exome AF: 0.0209

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000420

Gnomad NFE exome AF: 0.00343

Gnomad OTH exome AF: 0.00403

GnomAD4 exome AF: 0.00326 AC: 4560 AN: 1399946 Hom.: 25 Cov.: 22 AF XY: 0.00311 AC XY: 2178 AN XY: 699808

African (AFR) AF: 0.000870 AC: 28 AN: 32188

American (AMR) AF: 0.00102 AC: 45 AN: 44300

Ashkenazi Jewish (ASJ) AF: 0.0212 AC: 542 AN: 25622

East Asian (EAS) AF: 0.00 AC: 0 AN: 39382

South Asian (SAS) AF: 0.000864 AC: 73 AN: 84460

European-Finnish (FIN) AF: 0.000413 AC: 22 AN: 53286

Middle Eastern (MID) AF: 0.000887 AC: 5 AN: 5638

European-Non Finnish (NFE) AF: 0.00345 AC: 3642 AN: 1056790

Other (OTH) AF: 0.00348 AC: 203 AN: 58280

GnomAD4 genome AF: 0.00257 AC: 391 AN: 152230 Hom.: 0 Cov.: 32 AF XY: 0.00226 AC XY: 168 AN XY: 74426

African (AFR) AF: 0.000890 AC: 37 AN: 41550

American (AMR) AF: 0.000262 AC: 4 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3472

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

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4824

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10602

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

European-Non Finnish (NFE) AF: 0.00369 AC: 251 AN: 68006

Other (OTH) AF: 0.00142 AC: 3 AN: 2106

Alfa AF: 0.00398 Hom.: 1

Bravo AF: 0.00256

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	-1.0
CADD	Benign	0.0080
DANN	Benign	0.65
PhyloP100		-2.5
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: rs187039736; hg19: chr5-90159685;