rs142011700

Variant names:

• chr5-90629546-G-A
• rs142011700
• NM_032119.4:c.1839+7G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-90629546-G-A
• chr5-90629546-G-T

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.1839+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,575,870 control chromosomes in the GnomAD database, including 40 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 0.0087 (22 hom., cov: 31)
  • Exomes 𝑓: 0.0011 (18 hom.)
• Consequence: ADGRV1 NM_032119.4 splice_region, intron
• Scores: Splicing: ADA: 0.00001590
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.469
• Publications: 0 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=-0.83).
• BP6: Variant 5-90629546-G-A is Benign according to our data. Variant chr5-90629546-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 46297.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 = 0.00875 (1332/152236) while in subpopulation AFR AF = 0.0292 (1212/41524). AF 95% confidence interval is 0.0278. There are 22 homozygotes in GnomAd4. There are 634 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 22 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.1839+7G>A		splice_region intron	N/A	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.1938+7G>A		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.1839+7G>A		splice_region intron	N/A	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000640109.1	TSL:5	n.1942G>A		non_coding_transcript_exon	Exon 9 of 9
	ADGRV1	ENST00000504142.2	TSL:5	n.605+7G>A		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00874 AC: 1330 AN: 152118 Hom.: 21 Cov.: 31

Gnomad AFR AF: 0.0292

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00570

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.00258 AC: 595 AN: 230640 AF XY: 0.00204

Gnomad AFR exome AF: 0.0303

Gnomad AMR exome AF: 0.00254

Gnomad ASJ exome AF: 0.00186

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000321

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00107 AC: 1519 AN: 1423634 Hom.: 18 Cov.: 25 AF XY: 0.000932 AC XY: 660 AN XY: 707970

African (AFR) AF: 0.0312 AC: 995 AN: 31922

American (AMR) AF: 0.00273 AC: 112 AN: 41052

Ashkenazi Jewish (ASJ) AF: 0.00166 AC: 41 AN: 24754

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

South Asian (SAS) AF: 0.0000849 AC: 7 AN: 82478

European-Finnish (FIN) AF: 0.0000195 AC: 1 AN: 51396

Middle Eastern (MID) AF: 0.00374 AC: 21 AN: 5608

European-Non Finnish (NFE) AF: 0.000176 AC: 192 AN: 1088184

Other (OTH) AF: 0.00255 AC: 150 AN: 58856

GnomAD4 genome AF: 0.00875 AC: 1332 AN: 152236 Hom.: 22 Cov.: 31 AF XY: 0.00852 AC XY: 634 AN XY: 74436

African (AFR) AF: 0.0292 AC: 1212 AN: 41524

American (AMR) AF: 0.00569 AC: 87 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10606

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

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68028

Other (OTH) AF: 0.00663 AC: 14 AN: 2112

Alfa AF: 0.00344 Hom.: 2

Bravo AF: 0.0103

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.31
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000016
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: rs142011700; hg19: chr5-89925363;