NM_032119.4:c.11031C>T

Variant names:

• chr5-90750607-C-T
• rs75480336
• NM_032119.4:c.11031C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4 BP6_Very_Strong BP7 BS1 BS2

The NM_032119.4(ADGRV1):​c.11031C>T​(p.Asn3677Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,611,840 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0090 (17 hom., cov: 32)
  • Exomes 𝑓: 0.00093 (23 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.736
• 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: ClinGen, Orphanet
• Usher syndrome type 2C

  Inheritance: AR Classification: STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• 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=0.282).
• BP6: Variant 5-90750607-C-T is Benign according to our data. Variant chr5-90750607-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 46253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.736 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00899 (1369/152242) while in subpopulation AFR AF = 0.0315 (1308/41532). AF 95% confidence interval is 0.0301. There are 17 homozygotes in GnomAd4. There are 616 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	NM_032119.4	MANE Select	c.11031C>T	p.Asn3677Asn	synonymous	Exon 53 of 90	NP_115495.3
	ADGRV1	NR_003149.2		n.11047C>T		non_coding_transcript_exon	Exon 53 of 90

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.11031C>T	p.Asn3677Asn	synonymous	Exon 53 of 90	ENSP00000384582.2
	ADGRV1	ENST00000509621.1	TSL:1	n.3728C>T		non_coding_transcript_exon	Exon 21 of 26
	ADGRV1	ENST00000425867.3	TSL:5	c.162C>T	p.Asn54Asn	synonymous	Exon 2 of 38	ENSP00000392618.3

Frequencies

GnomAD3 genomes AF: 0.00901 AC: 1370 AN: 152124 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00282

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00226 AC: 563 AN: 248756 AF XY: 0.00176

Gnomad AFR exome AF: 0.0319

Gnomad AMR exome AF: 0.00154

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000557

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000798

Gnomad OTH exome AF: 0.000498

GnomAD4 exome AF: 0.000935 AC: 1364 AN: 1459598 Hom.: 23 Cov.: 29 AF XY: 0.000808 AC XY: 587 AN XY: 726186

African (AFR) AF: 0.0318 AC: 1063 AN: 33424

American (AMR) AF: 0.00163 AC: 73 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39636

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5758

European-Non Finnish (NFE) AF: 0.0000811 AC: 90 AN: 1110228

Other (OTH) AF: 0.00186 AC: 112 AN: 60284

GnomAD4 genome AF: 0.00899 AC: 1369 AN: 152242 Hom.: 17 Cov.: 32 AF XY: 0.00828 AC XY: 616 AN XY: 74428

African (AFR) AF: 0.0315 AC: 1308 AN: 41532

American (AMR) AF: 0.00281 AC: 43 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68028

Other (OTH) AF: 0.00379 AC: 8 AN: 2110

Alfa AF: 0.00491 Hom.: 6

Bravo AF: 0.0101

EpiCase AF: 0.000110

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	not provided (2)
-	-	1	Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	5.7
DANN	Benign	0.62
PhyloP100		0.74
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: rs75480336; hg19: chr5-90046424;