rs137853919

Variant names:

• chr5-90681308-C-T
• rs137853919
• NM_032119.4:c.5525-7C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-90681308-C-T
• chr5-90681308-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.5525-7C>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 0.00608 in 1,609,152 control chromosomes in the GnomAD database, including 53 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 0.0044 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0063 (51 hom.)
• Consequence: ADGRV1 NM_032119.4 splice_region, intron
• Scores: Splicing: ADA: 0.00002221
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:14 O:1
• Conservation: PhyloP100: 0.311
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 5-90681308-C-T is Benign according to our data. Variant chr5-90681308-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 46337.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00437 (663/151764) while in subpopulation SAS AF = 0.00955 (46/4816). AF 95% confidence interval is 0.00736. There are 2 homozygotes in GnomAd4. There are 326 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 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.5525-7C>T		splice_region intron	N/A	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.5624-7C>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.5525-7C>T		splice_region intron	N/A	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000640403.1	TSL:5	c.2816-7C>T		splice_region intron	N/A	ENSP00000492531.1	A0A1W2PRC7
	ADGRV1	ENST00000639431.1	TSL:5	n.265+5099C>T		intron	N/A	ENSP00000491057.1	A0A1W2PNS5

Frequencies

GnomAD3 genomes AF: 0.00437 AC: 663 AN: 151646 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000873

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00335

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00954

Gnomad FIN AF: 0.00517

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00687

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00516 AC: 1267 AN: 245678 AF XY: 0.00562

Gnomad AFR exome AF: 0.000906

Gnomad AMR exome AF: 0.00156

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00531

Gnomad NFE exome AF: 0.00675

Gnomad OTH exome AF: 0.00758

GnomAD4 exome AF: 0.00626 AC: 9123 AN: 1457388 Hom.: 51 Cov.: 31 AF XY: 0.00654 AC XY: 4735 AN XY: 724516

African (AFR) AF: 0.000721 AC: 24 AN: 33288

American (AMR) AF: 0.00175 AC: 77 AN: 44096

Ashkenazi Jewish (ASJ) AF: 0.000308 AC: 8 AN: 26008

East Asian (EAS) AF: 0.00 AC: 0 AN: 39632

South Asian (SAS) AF: 0.0103 AC: 874 AN: 85190

European-Finnish (FIN) AF: 0.00587 AC: 313 AN: 53330

Middle Eastern (MID) AF: 0.0138 AC: 79 AN: 5738

European-Non Finnish (NFE) AF: 0.00662 AC: 7344 AN: 1109896

Other (OTH) AF: 0.00671 AC: 404 AN: 60210

GnomAD4 genome AF: 0.00437 AC: 663 AN: 151764 Hom.: 2 Cov.: 32 AF XY: 0.00440 AC XY: 326 AN XY: 74118

African (AFR) AF: 0.000870 AC: 36 AN: 41382

American (AMR) AF: 0.00335 AC: 51 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00955 AC: 46 AN: 4816

European-Finnish (FIN) AF: 0.00517 AC: 54 AN: 10452

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

European-Non Finnish (NFE) AF: 0.00687 AC: 467 AN: 67952

Other (OTH) AF: 0.00426 AC: 9 AN: 2112

Alfa AF: 0.00568 Hom.: 0

Bravo AF: 0.00408

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00639

EpiControl AF: 0.00789

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not provided (7)
-	-	5	not specified (5)
-	-	1	ADGRV1-related disorder (1)
-	-	1	Febrile seizures, familial, 4;C2931213:Usher syndrome type 2C (1)
-	-	1	Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.8
DANN	Benign	0.48
PhyloP100		0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000022
dbscSNV1_RF	Benign	0.024
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: rs137853919; hg19: chr5-89977125;