rs7211982

Positions:

• chr17-15491058-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001204478.2(TVP23C-CDRT4):​c.463-50773G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 152,018 control chromosomes in the GnomAD database, including 20,764 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (20764 hom., cov: 32)
• Consequence: TVP23C-CDRT4 NM_001204478.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

Genes affected

TVP23C-CDRT4 (HGNC:42961): (TVP23C-CDRT4 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring TVP23C (trans-golgi network vesicle protein 23 homolog) and CDRT4 (CMT1A duplicated region transcript 4) genes on chromosome 17. Alternative splicing results in multiple transcript variants, one of which encodes a protein that shares sequence identity with the upstream gene product, but its C-terminus is distinct due to frameshifts relative to the downstream gene. [provided by RefSeq, Apr 2014]

TVP23C-CDRT4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TVP23C-CDRT4	NM_001204478.2	c.463-50773G>A		intron_variant			NP_001191407.1
TVP23C-CDRT4	NR_037924.2	n.353-50773G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TVP23C-CDRT4	ENST00000522212.6	c.463-50773G>A		intron_variant		2		ENSP00000429865.1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78265 AN: 151900 Hom.: 20760 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.539

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.515 AC: 78298 AN: 152018 Hom.: 20764 Cov.: 32 AF XY: 0.512 AC XY: 38040 AN XY: 74304

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.539

Alfa AF: 0.521 Hom.: 3539

Bravo AF: 0.500

Asia WGS AF: 0.407 AC: 1420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	10
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs7211982; hg19: chr17-15394372; COSMIC: COSV72154846;