rs7211982

Variant names:

• chr17-15491058-C-T
• rs7211982
• ENST00000522212.6:c.463-50773G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204478.2. 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
	TVP23C-CDRT4	NM_001204478.2		c.463-50773G>A		intron	N/A	NP_001191407.1	A0A0A6YYB9
	TVP23C-CDRT4	NR_037924.2		n.353-50773G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TVP23C-CDRT4	ENST00000522212.6	TSL:2	c.463-50773G>A		intron	N/A	ENSP00000429865.1
	TVP23C-CDRT4	ENST00000524205.3	TSL:2	c.-48+12040G>A		intron	N/A	ENSP00000452374.3	G3V5I9
	TVP23C-CDRT4	ENST00000481756.7	TSL:4	n.*204-50773G>A		intron	N/A	ENSP00000423249.3	E5RIS5

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

African (AFR) AF: 0.449 AC: 18610 AN: 41414

American (AMR) AF: 0.440 AC: 6730 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2078 AN: 3472

East Asian (EAS) AF: 0.258 AC: 1334 AN: 5170

South Asian (SAS) AF: 0.506 AC: 2435 AN: 4816

European-Finnish (FIN) AF: 0.561 AC: 5933 AN: 10576

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39360 AN: 67970

Other (OTH) AF: 0.539 AC: 1139 AN: 2112

Alfa AF: 0.519 Hom.: 3621

Bravo AF: 0.500

Asia WGS AF: 0.407 AC: 1420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	10
DANN	Benign	0.64
PhyloP100		1.0
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

Other links and lift over

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