rs17624033

Variant names:

• chr5-90745693-A-G
• rs17624033
• NM_032119.4:c.10872A>G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_032119.4(ADGRV1):​c.10872A>G​(p.Gln3624Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.041 in 1,612,324 control chromosomes in the GnomAD database, including 1,614 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (125 hom., cov: 32)
  • Exomes 𝑓: 0.042 (1489 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8 O:1
• Conservation: PhyloP100: 0.128
• Publications: 7 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 (REVEL=0.066).
• BP6: Variant 5-90745693-A-G is Benign according to our data. Variant chr5-90745693-A-G is described in ClinVar as Benign. ClinVar VariationId is 46252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.128 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0318 (4840/152296) while in subpopulation AMR AF = 0.0466 (713/15294). AF 95% confidence interval is 0.0438. There are 125 homozygotes in GnomAd4. There are 2280 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 125 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.10872A>G	p.Gln3624Gln	synonymous	Exon 52 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.10888A>G		non_coding_transcript_exon	Exon 52 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.10872A>G	p.Gln3624Gln	synonymous	Exon 52 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000509621.1	TSL:1	n.3569A>G		non_coding_transcript_exon	Exon 20 of 26
	ADGRV1	ENST00000425867.3	TSL:5	c.3A>G	p.Gln1Gln	synonymous	Exon 1 of 38	ENSP00000392618.3	A0A1X7SBU6

Frequencies

GnomAD3 genomes AF: 0.0318 AC: 4842 AN: 152178 Hom.: 125 Cov.: 32

Gnomad AFR AF: 0.00881

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0467

Gnomad ASJ AF: 0.0713

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.0187

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0447

Gnomad OTH AF: 0.0502

GnomAD2 exomes AF: 0.0312 AC: 7750 AN: 248594 AF XY: 0.0317

Gnomad AFR exome AF: 0.00698

Gnomad AMR exome AF: 0.0272

Gnomad ASJ exome AF: 0.0623

Gnomad EAS exome AF: 0.0000557

Gnomad FIN exome AF: 0.0200

Gnomad NFE exome AF: 0.0434

Gnomad OTH exome AF: 0.0382

GnomAD4 exome AF: 0.0420 AC: 61301 AN: 1460028 Hom.: 1489 Cov.: 29 AF XY: 0.0413 AC XY: 30017 AN XY: 726416

African (AFR) AF: 0.00783 AC: 262 AN: 33456

American (AMR) AF: 0.0288 AC: 1287 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0629 AC: 1644 AN: 26122

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39644

South Asian (SAS) AF: 0.0177 AC: 1522 AN: 86230

European-Finnish (FIN) AF: 0.0217 AC: 1154 AN: 53164

Middle Eastern (MID) AF: 0.0472 AC: 271 AN: 5744

European-Non Finnish (NFE) AF: 0.0474 AC: 52673 AN: 1110634

Other (OTH) AF: 0.0412 AC: 2485 AN: 60320

GnomAD4 genome AF: 0.0318 AC: 4840 AN: 152296 Hom.: 125 Cov.: 32 AF XY: 0.0306 AC XY: 2280 AN XY: 74460

African (AFR) AF: 0.00878 AC: 365 AN: 41572

American (AMR) AF: 0.0466 AC: 713 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0713 AC: 247 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.0145 AC: 70 AN: 4818

European-Finnish (FIN) AF: 0.0187 AC: 199 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0447 AC: 3041 AN: 68014

Other (OTH) AF: 0.0497 AC: 105 AN: 2112

Alfa AF: 0.0428 Hom.: 500

Bravo AF: 0.0344

Asia WGS AF: 0.00895 AC: 32 AN: 3478

EpiCase AF: 0.0477

EpiControl AF: 0.0463

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.3
DANN	Benign	0.30
PhyloP100		0.13
PromoterAI		-0.0022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs17624033; hg19: chr5-90041510;