5-90706403-C-CTT

Variant names:

• chr5-90706402-TC-TCT
• rs60522638
• NM_032119.4:c.8730+21dupT

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+21dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (35884 hom., cov: 0)
  • Exomes 𝑓: 0.45 (13569 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADGRV1 NM_032119.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.0450
• 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 -16 ACMG points.

• BP6: Variant 5-90706402-TC-TCT is Benign according to our data. Variant chr5-90706403-C-CT is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 197047.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 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+21dupT		intron	N/A	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.8746+21dupT		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+9_8730+10insT		intron	N/A	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000509621.1	TSL:1	n.1427+9_1427+10insT		intron	N/A
	ADGRV1	ENST00000640403.1	TSL:5	c.6021+9_6021+10insT		intron	N/A	ENSP00000492531.1	A0A1W2PRC7

Frequencies

GnomAD3 genomes AF: 0.700 AC: 102421 AN: 146356 Hom.: 35860 Cov.: 0

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.708

GnomAD2 exomes AF: 0.471 AC: 52545 AN: 111634 AF XY: 0.467

Gnomad AFR exome AF: 0.509

Gnomad AMR exome AF: 0.482

Gnomad ASJ exome AF: 0.461

Gnomad EAS exome AF: 0.492

Gnomad FIN exome AF: 0.476

Gnomad NFE exome AF: 0.459

Gnomad OTH exome AF: 0.466

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.450 AC: 545934 AN: 1213242 Hom.: 13569 Cov.: 25 AF XY: 0.449 AC XY: 269704 AN XY: 600146

African (AFR) AF: 0.495 AC: 12520 AN: 25312

American (AMR) AF: 0.448 AC: 10494 AN: 23430

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 9432 AN: 20984

East Asian (EAS) AF: 0.482 AC: 15951 AN: 33102

South Asian (SAS) AF: 0.461 AC: 29244 AN: 63472

European-Finnish (FIN) AF: 0.444 AC: 20155 AN: 45412

Middle Eastern (MID) AF: 0.510 AC: 2494 AN: 4886

European-Non Finnish (NFE) AF: 0.447 AC: 422531 AN: 946134

Other (OTH) AF: 0.458 AC: 23113 AN: 50510

GnomAD4 genome AF: 0.700 AC: 102477 AN: 146434 Hom.: 35884 Cov.: 0 AF XY: 0.700 AC XY: 49842 AN XY: 71218

African (AFR) AF: 0.806 AC: 32244 AN: 40006

American (AMR) AF: 0.714 AC: 10421 AN: 14594

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2257 AN: 3406

East Asian (EAS) AF: 0.792 AC: 3914 AN: 4944

South Asian (SAS) AF: 0.726 AC: 3344 AN: 4608

European-Finnish (FIN) AF: 0.626 AC: 5756 AN: 9194

Middle Eastern (MID) AF: 0.682 AC: 199 AN: 292

European-Non Finnish (NFE) AF: 0.636 AC: 42301 AN: 66472

Other (OTH) AF: 0.711 AC: 1431 AN: 2012

Alfa AF: 0.434 Hom.: 717

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	1	Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.045
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs60522638; hg19: chr5-90002219;