NM_032119.4:c.10769+9A>G

Variant names:

• chr5-90745274-A-G
• rs116184119
• NM_032119.4:c.10769+9A>G

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.10769+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00788 in 1,540,212 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0063 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0080 (45 hom.)
• Consequence: ADGRV1 NM_032119.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: -0.387
• Publications: 2 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 5-90745274-A-G is Benign according to our data. Variant chr5-90745274-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 46251.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0063 (959/152284) while in subpopulation AMR AF = 0.0105 (161/15294). AF 95% confidence interval is 0.0092. There are 6 homozygotes in GnomAd4. There are 446 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 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.10769+9A>G		intron	N/A	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.10785+9A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.10769+9A>G		intron	N/A	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000509621.1	TSL:1	n.3466+9A>G		intron	N/A
	ADGRV1	ENST00000639431.1	TSL:5	n.265+69065A>G		intron	N/A	ENSP00000491057.1	A0A1W2PNS5

Frequencies

GnomAD3 genomes AF: 0.00630 AC: 959 AN: 152166 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00882

Gnomad OTH AF: 0.00812

GnomAD2 exomes AF: 0.00685 AC: 1472 AN: 214876 AF XY: 0.00705

Gnomad AFR exome AF: 0.000807

Gnomad AMR exome AF: 0.00583

Gnomad ASJ exome AF: 0.0308

Gnomad EAS exome AF: 0.0000604

Gnomad FIN exome AF: 0.00254

Gnomad NFE exome AF: 0.00903

Gnomad OTH exome AF: 0.00469

GnomAD4 exome AF: 0.00805 AC: 11171 AN: 1387928 Hom.: 45 Cov.: 22 AF XY: 0.00801 AC XY: 5517 AN XY: 689056

African (AFR) AF: 0.000957 AC: 30 AN: 31346

American (AMR) AF: 0.00582 AC: 221 AN: 37972

Ashkenazi Jewish (ASJ) AF: 0.0252 AC: 610 AN: 24246

East Asian (EAS) AF: 0.0000256 AC: 1 AN: 39070

South Asian (SAS) AF: 0.00225 AC: 174 AN: 77356

European-Finnish (FIN) AF: 0.00301 AC: 128 AN: 42518

Middle Eastern (MID) AF: 0.00339 AC: 17 AN: 5018

European-Non Finnish (NFE) AF: 0.00886 AC: 9500 AN: 1072768

Other (OTH) AF: 0.00850 AC: 490 AN: 57634

GnomAD4 genome AF: 0.00630 AC: 959 AN: 152284 Hom.: 6 Cov.: 32 AF XY: 0.00599 AC XY: 446 AN XY: 74462

African (AFR) AF: 0.00144 AC: 60 AN: 41570

American (AMR) AF: 0.0105 AC: 161 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0291 AC: 101 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10606

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

European-Non Finnish (NFE) AF: 0.00882 AC: 600 AN: 68010

Other (OTH) AF: 0.00803 AC: 17 AN: 2116

Alfa AF: 0.00648 Hom.: 2

Bravo AF: 0.00645

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not provided (7)
-	-	5	not specified (5)
-	-	1	Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.1
DANN	Benign	0.73
PhyloP100		-0.39
PromoterAI		0.0081	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs116184119; hg19: chr5-90041091;