chr5-90693935-C-T

Variant names:

• chr5-90693935-C-T
• rs111033429
• NM_032119.4:c.7179C>T

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.7179C>T​(p.Asp2393Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00944 in 1,597,582 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0073 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0097 (87 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.197
• Publications: 3 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=-0.58).
• BP6: Variant 5-90693935-C-T is Benign according to our data. Variant chr5-90693935-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 46364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.197 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00732 (1115/152270) while in subpopulation NFE AF = 0.0109 (743/68020). AF 95% confidence interval is 0.0103. There are 9 homozygotes in GnomAd4. There are 553 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 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.7179C>T	p.Asp2393Asp	synonymous	Exon 33 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.7195C>T		non_coding_transcript_exon	Exon 33 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.7179C>T	p.Asp2393Asp	synonymous	Exon 33 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000640403.1	TSL:5	c.4470C>T	p.Asp1490Asp	synonymous	Exon 23 of 29	ENSP00000492531.1	A0A1W2PRC7
	ADGRV1	ENST00000639473.1	TSL:5	n.2638C>T		non_coding_transcript_exon	Exon 13 of 23

Frequencies

GnomAD3 genomes AF: 0.00733 AC: 1115 AN: 152152 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00229

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0215

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00817 AC: 1969 AN: 240976 AF XY: 0.00824

Gnomad AFR exome AF: 0.00163

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00250

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0221

Gnomad NFE exome AF: 0.0125

Gnomad OTH exome AF: 0.00900

GnomAD4 exome AF: 0.00966 AC: 13964 AN: 1445312 Hom.: 87 Cov.: 30 AF XY: 0.00931 AC XY: 6671 AN XY: 716392

African (AFR) AF: 0.00133 AC: 44 AN: 33064

American (AMR) AF: 0.00139 AC: 61 AN: 43754

Ashkenazi Jewish (ASJ) AF: 0.00289 AC: 73 AN: 25280

East Asian (EAS) AF: 0.00 AC: 0 AN: 39384

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84568

European-Finnish (FIN) AF: 0.0239 AC: 1261 AN: 52846

Middle Eastern (MID) AF: 0.000353 AC: 2 AN: 5662

European-Non Finnish (NFE) AF: 0.0110 AC: 12126 AN: 1101208

Other (OTH) AF: 0.00665 AC: 396 AN: 59546

GnomAD4 genome AF: 0.00732 AC: 1115 AN: 152270 Hom.: 9 Cov.: 32 AF XY: 0.00743 AC XY: 553 AN XY: 74434

African (AFR) AF: 0.00229 AC: 95 AN: 41556

American (AMR) AF: 0.00196 AC: 30 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

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

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.0215 AC: 228 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0109 AC: 743 AN: 68020

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.0100 Hom.: 14

Bravo AF: 0.00602

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not provided (6)
-	-	4	not specified (4)
-	-	1	Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.3
DANN	Benign	0.50
PhyloP100		0.20
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)		0.050		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: rs111033429; hg19: chr5-89989752;