chr5-90815704-A-G

Variant names:

• chr5-90815704-A-G
• rs41304884
• NM_032119.4:c.16164A>G

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.16164A>G​(p.Arg5388Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 1,566,476 control chromosomes in the GnomAD database, including 329 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (17 hom., cov: 32)
  • Exomes 𝑓: 0.017 (312 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.885
• Publications: 5 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=-0.84).
• BP6: Variant 5-90815704-A-G is Benign according to our data. Variant chr5-90815704-A-G is described in ClinVar as Benign. ClinVar VariationId is 46283.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.885 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0137 (2087/152280) while in subpopulation SAS AF = 0.0483 (233/4826). AF 95% confidence interval is 0.0432. There are 17 homozygotes in GnomAd4. There are 1043 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 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.16164A>G	p.Arg5388Arg	synonymous	Exon 75 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.16180A>G		non_coding_transcript_exon	Exon 75 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.16164A>G	p.Arg5388Arg	synonymous	Exon 75 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000638510.1	TSL:1	n.3431A>G		non_coding_transcript_exon	Exon 11 of 26
	ADGRV1	ENST00000425867.3	TSL:5	c.5118A>G	p.Arg1706Arg	synonymous	Exon 23 of 38	ENSP00000392618.3	A0A1X7SBU6

Frequencies

GnomAD3 genomes AF: 0.0137 AC: 2092 AN: 152162 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.00866

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0484

Gnomad FIN AF: 0.00923

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0166

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.0171 AC: 3139 AN: 184080 AF XY: 0.0193

Gnomad AFR exome AF: 0.00873

Gnomad AMR exome AF: 0.0112

Gnomad ASJ exome AF: 0.00867

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00888

Gnomad NFE exome AF: 0.0168

Gnomad OTH exome AF: 0.0228

GnomAD4 exome AF: 0.0172 AC: 24315 AN: 1414196 Hom.: 312 Cov.: 27 AF XY: 0.0182 AC XY: 12725 AN XY: 699588

African (AFR) AF: 0.00857 AC: 278 AN: 32444

American (AMR) AF: 0.0109 AC: 415 AN: 38086

Ashkenazi Jewish (ASJ) AF: 0.00765 AC: 194 AN: 25348

East Asian (EAS) AF: 0.0000796 AC: 3 AN: 37710

South Asian (SAS) AF: 0.0462 AC: 3702 AN: 80166

European-Finnish (FIN) AF: 0.00836 AC: 426 AN: 50986

Middle Eastern (MID) AF: 0.0477 AC: 272 AN: 5708

European-Non Finnish (NFE) AF: 0.0166 AC: 17972 AN: 1084908

Other (OTH) AF: 0.0179 AC: 1053 AN: 58840

GnomAD4 genome AF: 0.0137 AC: 2087 AN: 152280 Hom.: 17 Cov.: 32 AF XY: 0.0140 AC XY: 1043 AN XY: 74468

African (AFR) AF: 0.00864 AC: 359 AN: 41560

American (AMR) AF: 0.0126 AC: 192 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00980 AC: 34 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.0483 AC: 233 AN: 4826

European-Finnish (FIN) AF: 0.00923 AC: 98 AN: 10612

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0166 AC: 1128 AN: 68022

Other (OTH) AF: 0.0128 AC: 27 AN: 2114

Alfa AF: 0.0152 Hom.: 33

Bravo AF: 0.0129

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.65
DANN	Benign	0.38
PhyloP100		-0.89
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: rs41304884; hg19: chr5-90111521; COSMIC: COSV107509518;