rs6880570

Variant names:

• chr5-90705551-T-G
• rs6880570
• NM_032119.4:c.8538T>G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4 BP6_Very_Strong BP7 BA1

The NM_032119.4(ADGRV1):​c.8538T>G​(p.Leu2846Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,612,200 control chromosomes in the GnomAD database, including 21,268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3815 hom., cov: 32)
  • Exomes 𝑓: 0.14 (17453 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 1.48
• Publications: 19 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.236).
• BP6: Variant 5-90705551-T-G is Benign according to our data. Variant chr5-90705551-T-G is described in ClinVar as Benign. ClinVar VariationId is 46390.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.48 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 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.8538T>G	p.Leu2846Leu	synonymous	Exon 37 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.8554T>G		non_coding_transcript_exon	Exon 37 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.8538T>G	p.Leu2846Leu	synonymous	Exon 37 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000509621.1	TSL:1	n.1235T>G		non_coding_transcript_exon	Exon 5 of 26
	ADGRV1	ENST00000640403.1	TSL:5	c.5829T>G	p.Leu1943Leu	synonymous	Exon 27 of 29	ENSP00000492531.1	A0A1W2PRC7

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30743 AN: 151998 Hom.: 3796 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.202

GnomAD2 exomes AF: 0.180 AC: 44738 AN: 248916 AF XY: 0.176

Gnomad AFR exome AF: 0.339

Gnomad AMR exome AF: 0.143

Gnomad ASJ exome AF: 0.215

Gnomad EAS exome AF: 0.409

Gnomad FIN exome AF: 0.171

Gnomad NFE exome AF: 0.126

Gnomad OTH exome AF: 0.162

GnomAD4 exome AF: 0.142 AC: 207202 AN: 1460084 Hom.: 17453 Cov.: 32 AF XY: 0.143 AC XY: 104105 AN XY: 726348

African (AFR) AF: 0.345 AC: 11530 AN: 33426

American (AMR) AF: 0.146 AC: 6538 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 5462 AN: 26114

East Asian (EAS) AF: 0.372 AC: 14765 AN: 39680

South Asian (SAS) AF: 0.197 AC: 16937 AN: 86162

European-Finnish (FIN) AF: 0.163 AC: 8697 AN: 53386

Middle Eastern (MID) AF: 0.176 AC: 1007 AN: 5732

European-Non Finnish (NFE) AF: 0.119 AC: 131904 AN: 1110550

Other (OTH) AF: 0.172 AC: 10362 AN: 60324

GnomAD4 genome AF: 0.202 AC: 30797 AN: 152116 Hom.: 3815 Cov.: 32 AF XY: 0.205 AC XY: 15274 AN XY: 74394

African (AFR) AF: 0.333 AC: 13809 AN: 41462

American (AMR) AF: 0.160 AC: 2452 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 715 AN: 3468

East Asian (EAS) AF: 0.405 AC: 2092 AN: 5166

South Asian (SAS) AF: 0.202 AC: 974 AN: 4822

European-Finnish (FIN) AF: 0.162 AC: 1714 AN: 10592

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8458 AN: 68006

Other (OTH) AF: 0.210 AC: 442 AN: 2108

Alfa AF: 0.153 Hom.: 7208

Bravo AF: 0.210

Asia WGS AF: 0.335 AC: 1163 AN: 3478

EpiCase AF: 0.130

EpiControl AF: 0.131

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	2	Usher syndrome type 2C (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	6.0
DANN	Benign	0.84
PhyloP100		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6880570; hg19: chr5-90001368; COSMIC: COSV67978733;