rs10067298

Variant names:

• chr5-90676112-A-G
• rs10067298
• NM_032119.4:c.5346A>G

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.5346A>G​(p.Gly1782Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00386 in 1,603,616 control chromosomes in the GnomAD database, including 198 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (104 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (94 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 2.03
• 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 5-90676112-A-G is Benign according to our data. Variant chr5-90676112-A-G is described in ClinVar as Benign. ClinVar VariationId is 46335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0724 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.5346A>G	p.Gly1782Gly	synonymous	Exon 25 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.5445A>G		non_coding_transcript_exon	Exon 25 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.5346A>G	p.Gly1782Gly	synonymous	Exon 25 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000450321.2	TSL:1	n.*464A>G		non_coding_transcript_exon	Exon 5 of 6	ENSP00000492054.1	A0A1W2PR51
	ADGRV1	ENST00000450321.2	TSL:1	n.*464A>G		3_prime_UTR	Exon 5 of 6	ENSP00000492054.1	A0A1W2PR51

Frequencies

GnomAD3 genomes AF: 0.0213 AC: 3245 AN: 152202 Hom.: 105 Cov.: 32

Gnomad AFR AF: 0.0747

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00694

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0124

GnomAD2 exomes AF: 0.00492 AC: 1183 AN: 240492 AF XY: 0.00379

Gnomad AFR exome AF: 0.0714

Gnomad AMR exome AF: 0.00293

Gnomad ASJ exome AF: 0.000102

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000193

Gnomad OTH exome AF: 0.00103

GnomAD4 exome AF: 0.00202 AC: 2933 AN: 1451296 Hom.: 94 Cov.: 27 AF XY: 0.00172 AC XY: 1239 AN XY: 721802

African (AFR) AF: 0.0700 AC: 2319 AN: 33146

American (AMR) AF: 0.00355 AC: 156 AN: 43920

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25870

East Asian (EAS) AF: 0.00 AC: 0 AN: 39366

South Asian (SAS) AF: 0.0000942 AC: 8 AN: 84912

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53142

Middle Eastern (MID) AF: 0.00191 AC: 10 AN: 5228

European-Non Finnish (NFE) AF: 0.000153 AC: 169 AN: 1105824

Other (OTH) AF: 0.00453 AC: 271 AN: 59888

GnomAD4 genome AF: 0.0213 AC: 3250 AN: 152320 Hom.: 104 Cov.: 32 AF XY: 0.0202 AC XY: 1508 AN XY: 74480

African (AFR) AF: 0.0746 AC: 3101 AN: 41572

American (AMR) AF: 0.00686 AC: 105 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68020

Other (OTH) AF: 0.0123 AC: 26 AN: 2116

Alfa AF: 0.00974 Hom.: 24

Bravo AF: 0.0238

Asia WGS AF: 0.00434 AC: 15 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	1	Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	12
DANN	Benign	0.70
PhyloP100		2.0
Mutation Taster		=95/5	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: rs10067298; hg19: chr5-89971929;