5-90706403-C-CTT

Variant names:

• chr5-90706403-C-CTT
• rs60522638
• NM_032119.4:c.8730+20_8730+21dupTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP6_Moderate BS1

The NM_032119.4(ADGRV1):​c.8730+20_8730+21dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00851 in 1,355,026 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0095 (0 hom.)
• Consequence: ADGRV1 NM_032119.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0450

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 5-90706403-C-CTT is Benign according to our data. Variant chr5-90706403-C-CTT is described in ClinVar as [Benign]. Clinvar id is 1165478.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00951 (11493/1208528) while in subpopulation AFR AF= 0.0155 (385/24878). AF 95% confidence interval is 0.0142. There are 0 homozygotes in gnomad4_exome. There are 5571 alleles in male gnomad4_exome subpopulation. Median coverage is 25. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.8730+20_8730+21dupTT		intron_variant	Intron 38 of 89	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.8730+9_8730+10insTT		intron_variant	Intron 38 of 89	1	NM_032119.4	ENSP00000384582.2

Frequencies

GnomAD3 genomes AF: 0.000225 AC: 33 AN: 146426 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000351

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000343

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000605

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000109

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000150

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00951 AC: 11493 AN: 1208528 Hom.: 0 Cov.: 25 AF XY: 0.00932 AC XY: 5571 AN XY: 597936

Gnomad4 AFR exome AF: 0.0155

Gnomad4 AMR exome AF: 0.0107

Gnomad4 ASJ exome AF: 0.00994

Gnomad4 EAS exome AF: 0.00886

Gnomad4 SAS exome AF: 0.0111

Gnomad4 FIN exome AF: 0.00538

Gnomad4 NFE exome AF: 0.00940

Gnomad4 OTH exome AF: 0.0101

GnomAD4 genome AF: 0.000225 AC: 33 AN: 146498 Hom.: 0 Cov.: 0 AF XY: 0.000267 AC XY: 19 AN XY: 71250

Gnomad4 AFR AF: 0.000350

Gnomad4 AMR AF: 0.000342

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000607

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000109

Gnomad4 NFE AF: 0.000150

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 12, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs60522638; hg19: chr5-90002220;