NM_032119.4:c.8730+10_8730+11insC

Variant names:

• chr5-90706404-T-TC
• rs377585302
• NM_032119.4:c.8730+10_8730+11insC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_032119.4(ADGRV1):​c.8730+10_8730+11insC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00583 in 701,856 control chromosomes in the GnomAD database, including 82 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.071 (33 hom., cov: 31)
  • Exomes 𝑓: 0.0044 (49 hom.)
• Consequence: ADGRV1 NM_032119.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.54
• 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: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
• 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 -16 ACMG points.

• BP6: Variant 5-90706404-T-TC is Benign according to our data. Variant chr5-90706404-T-TC is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 46397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

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.8730+10_8730+11insC		intron	N/A	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.8746+10_8746+11insC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.8730+10_8730+11insC		intron	N/A	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000509621.1	TSL:1	n.1427+10_1427+11insC		intron	N/A
	ADGRV1	ENST00000640403.1	TSL:5	c.6021+10_6021+11insC		intron	N/A	ENSP00000492531.1	A0A1W2PRC7

Frequencies

GnomAD3 genomes AF: 0.0703 AC: 1047 AN: 14892 Hom.: 31 Cov.: 31

Gnomad AFR AF: 0.0632

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000690

Gnomad OTH AF: 0.157

GnomAD2 exomes AF: 0.0669 AC: 1799 AN: 26884 AF XY: 0.0563

Gnomad AFR exome AF: 0.0200

Gnomad AMR exome AF: 0.327

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.120

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000612

Gnomad OTH exome AF: 0.0531

GnomAD4 exome AF: 0.00442 AC: 3037 AN: 686940 Hom.: 49 Cov.: 30 AF XY: 0.00406 AC XY: 1374 AN XY: 338096

African (AFR) AF: 0.00171 AC: 31 AN: 18160

American (AMR) AF: 0.130 AC: 2318 AN: 17784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11436

East Asian (EAS) AF: 0.0184 AC: 423 AN: 22964

South Asian (SAS) AF: 0.00135 AC: 49 AN: 36286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3570

European-Non Finnish (NFE) AF: 0.0000655 AC: 34 AN: 518906

Other (OTH) AF: 0.00621 AC: 182 AN: 29326

GnomAD4 genome AF: 0.0709 AC: 1057 AN: 14916 Hom.: 33 Cov.: 31 AF XY: 0.0813 AC XY: 592 AN XY: 7282

African (AFR) AF: 0.0631 AC: 86 AN: 1362

American (AMR) AF: 0.357 AC: 850 AN: 2380

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 368

East Asian (EAS) AF: 0.210 AC: 83 AN: 396

South Asian (SAS) AF: 0.0136 AC: 5 AN: 368

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1086

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 22

European-Non Finnish (NFE) AF: 0.000690 AC: 6 AN: 8700

Other (OTH) AF: 0.157 AC: 27 AN: 172

Alfa AF: 0.00556 Hom.: 2

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Febrile seizures, familial, 4;C2931213:Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5
Mutation Taster		=23/77	disease causing (long InDel)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs377585302; hg19: chr5-90002221; COSMIC: COSV107509595;