rs139278305

Variant names:

• chr5-90694707-C-T
• rs139278305
• NM_032119.4:c.7945+6C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-90694707-C-T
• chr5-90694707-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_032119.4(ADGRV1):​c.7945+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 1,554,742 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (30 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (25 hom.)
• Consequence: ADGRV1 NM_032119.4 splice_region, intron
• Scores: Splicing: ADA: 0.00002363
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.724
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 5-90694707-C-T is Benign according to our data. Variant chr5-90694707-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 46382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0101 (1539/152156) while in subpopulation AFR AF = 0.0351 (1458/41508). AF 95% confidence interval is 0.0336. There are 30 homozygotes in GnomAd4. There are 750 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 30 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.7945+6C>T		splice_region intron	N/A	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.7961+6C>T		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.7945+6C>T		splice_region intron	N/A	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000509621.1	TSL:1	n.642+6C>T		splice_region intron	N/A
	ADGRV1	ENST00000640403.1	TSL:5	c.5236+6C>T		splice_region intron	N/A	ENSP00000492531.1	A0A1W2PRC7

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1537 AN: 152038 Hom.: 30 Cov.: 32

Gnomad AFR AF: 0.0352

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00348

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00304 AC: 610 AN: 200538 AF XY: 0.00235

Gnomad AFR exome AF: 0.0352

Gnomad AMR exome AF: 0.00241

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000189

Gnomad OTH exome AF: 0.000428

GnomAD4 exome AF: 0.00108 AC: 1521 AN: 1402586 Hom.: 25 Cov.: 34 AF XY: 0.000986 AC XY: 682 AN XY: 691436

African (AFR) AF: 0.0346 AC: 1090 AN: 31516

American (AMR) AF: 0.00235 AC: 85 AN: 36172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22062

East Asian (EAS) AF: 0.00 AC: 0 AN: 39198

South Asian (SAS) AF: 0.0000532 AC: 4 AN: 75190

European-Finnish (FIN) AF: 0.0000196 AC: 1 AN: 51020

Middle Eastern (MID) AF: 0.00423 AC: 23 AN: 5442

European-Non Finnish (NFE) AF: 0.000172 AC: 186 AN: 1084226

Other (OTH) AF: 0.00229 AC: 132 AN: 57760

GnomAD4 genome AF: 0.0101 AC: 1539 AN: 152156 Hom.: 30 Cov.: 32 AF XY: 0.0101 AC XY: 750 AN XY: 74384

African (AFR) AF: 0.0351 AC: 1458 AN: 41508

American (AMR) AF: 0.00347 AC: 53 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68016

Other (OTH) AF: 0.00427 AC: 9 AN: 2108

Alfa AF: 0.00775 Hom.: 8

Bravo AF: 0.0115

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	4	not provided (4)
-	-	1	Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	14
DANN	Benign	0.45
PhyloP100		0.72
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000024
dbscSNV1_RF	Benign	0.0
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: rs139278305; hg19: chr5-89990524;