5-90685823-G-A

Variant names:

• chr5-90685823-G-A
• rs190981860
• NM_032119.4:c.6318G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_032119.4(ADGRV1):​c.6318G>A​(p.Ala2106Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0029 in 1,611,132 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A2106A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0021 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0030 (26 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.0830
• Publications: 4 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 5-90685823-G-A is Benign according to our data. Variant chr5-90685823-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 46352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.083 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00207 (315/152058) while in subpopulation SAS AF = 0.0194 (93/4802). AF 95% confidence interval is 0.0162. There are 1 homozygotes in GnomAd4. There are 179 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 26 AD,AR 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.6318G>A	p.Ala2106Ala	synonymous	Exon 29 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.6417G>A		non_coding_transcript_exon	Exon 29 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.6318G>A	p.Ala2106Ala	synonymous	Exon 29 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000640403.1	TSL:5	c.3609G>A	p.Ala1203Ala	synonymous	Exon 19 of 29	ENSP00000492531.1	A0A1W2PRC7
	ADGRV1	ENST00000639473.1	TSL:5	n.1777G>A		non_coding_transcript_exon	Exon 9 of 23

Frequencies

GnomAD3 genomes AF: 0.00207 AC: 315 AN: 151940 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000363

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.0194

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00206

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00381 AC: 943 AN: 247598 AF XY: 0.00477

Gnomad AFR exome AF: 0.000194

Gnomad AMR exome AF: 0.00182

Gnomad ASJ exome AF: 0.000398

Gnomad EAS exome AF: 0.000279

Gnomad FIN exome AF: 0.0000945

Gnomad NFE exome AF: 0.00228

Gnomad OTH exome AF: 0.00283

GnomAD4 exome AF: 0.00299 AC: 4359 AN: 1459074 Hom.: 26 Cov.: 31 AF XY: 0.00351 AC XY: 2548 AN XY: 725884

African (AFR) AF: 0.000568 AC: 19 AN: 33458

American (AMR) AF: 0.00200 AC: 89 AN: 44586

Ashkenazi Jewish (ASJ) AF: 0.000652 AC: 17 AN: 26084

East Asian (EAS) AF: 0.000555 AC: 22 AN: 39626

South Asian (SAS) AF: 0.0183 AC: 1572 AN: 85996

European-Finnish (FIN) AF: 0.000170 AC: 9 AN: 52824

Middle Eastern (MID) AF: 0.00850 AC: 49 AN: 5762

European-Non Finnish (NFE) AF: 0.00213 AC: 2365 AN: 1110482

Other (OTH) AF: 0.00360 AC: 217 AN: 60256

GnomAD4 genome AF: 0.00207 AC: 315 AN: 152058 Hom.: 1 Cov.: 31 AF XY: 0.00241 AC XY: 179 AN XY: 74326

African (AFR) AF: 0.000362 AC: 15 AN: 41462

American (AMR) AF: 0.00347 AC: 53 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.000967 AC: 5 AN: 5172

South Asian (SAS) AF: 0.0194 AC: 93 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10566

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00206 AC: 140 AN: 68000

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.00130 Hom.: 0

Bravo AF: 0.00174

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.00246

EpiControl AF: 0.00303

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not provided (5)
-	-	3	not specified (3)
-	-	1	Febrile seizures, familial, 4;C2931213:Usher syndrome type 2C (1)
-	-	1	Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.32
PhyloP100		0.083
Mutation Taster		=97/3	polymorphism

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: rs190981860; hg19: chr5-89981640; COSMIC: COSV67980739;