chr5-90675436-G-A

Variant names:

• chr5-90675436-G-A
• rs41303346
• NM_032119.4:c.5304G>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.5304G>A​(p.Glu1768Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 1,612,602 control chromosomes in the GnomAD database, including 332 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (20 hom., cov: 32)
  • Exomes 𝑓: 0.019 (312 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.370
• Publications: 2 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=-0.7).
• BP6: Variant 5-90675436-G-A is Benign according to our data. Variant chr5-90675436-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 46334.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.37 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0133 (2026/152240) while in subpopulation NFE AF = 0.0209 (1420/68016). AF 95% confidence interval is 0.02. There are 20 homozygotes in GnomAd4. There are 924 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 20 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.5304G>A	p.Glu1768Glu	synonymous	Exon 24 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.5403G>A		non_coding_transcript_exon	Exon 24 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.5304G>A	p.Glu1768Glu	synonymous	Exon 24 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000450321.2	TSL:1	n.*422G>A		non_coding_transcript_exon	Exon 4 of 6	ENSP00000492054.1	A0A1W2PR51
	ADGRV1	ENST00000450321.2	TSL:1	n.*422G>A		3_prime_UTR	Exon 4 of 6	ENSP00000492054.1	A0A1W2PR51

Frequencies

GnomAD3 genomes AF: 0.0133 AC: 2026 AN: 152122 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.00440

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0209

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.0132 AC: 3259 AN: 247174 AF XY: 0.0133

Gnomad AFR exome AF: 0.00430

Gnomad AMR exome AF: 0.00942

Gnomad ASJ exome AF: 0.0154

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0161

Gnomad NFE exome AF: 0.0195

Gnomad OTH exome AF: 0.0165

GnomAD4 exome AF: 0.0190 AC: 27811 AN: 1460362 Hom.: 312 Cov.: 30 AF XY: 0.0185 AC XY: 13470 AN XY: 726352

African (AFR) AF: 0.00353 AC: 118 AN: 33462

American (AMR) AF: 0.0101 AC: 451 AN: 44528

Ashkenazi Jewish (ASJ) AF: 0.0160 AC: 417 AN: 26100

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39682

South Asian (SAS) AF: 0.00355 AC: 305 AN: 85972

European-Finnish (FIN) AF: 0.0170 AC: 906 AN: 53348

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5768

European-Non Finnish (NFE) AF: 0.0221 AC: 24518 AN: 1111168

Other (OTH) AF: 0.0179 AC: 1082 AN: 60334

GnomAD4 genome AF: 0.0133 AC: 2026 AN: 152240 Hom.: 20 Cov.: 32 AF XY: 0.0124 AC XY: 924 AN XY: 74440

African (AFR) AF: 0.00438 AC: 182 AN: 41532

American (AMR) AF: 0.0117 AC: 179 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3470

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

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4826

European-Finnish (FIN) AF: 0.0136 AC: 144 AN: 10592

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

European-Non Finnish (NFE) AF: 0.0209 AC: 1420 AN: 68016

Other (OTH) AF: 0.0114 AC: 24 AN: 2114

Alfa AF: 0.0176 Hom.: 21

Bravo AF: 0.0132

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	3	not specified (3)
-	-	1	Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.5
DANN	Benign	0.49
PhyloP100		0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs41303346; hg19: chr5-89971253;