rs6597292

Variant names:

• chr6-7975026-T-G
• rs6597292
• ENST00000439343.2:n.372+51341A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000439343.2(BLOC1S5-TXNDC5):​n.372+51341A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,002 control chromosomes in the GnomAD database, including 11,760 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 0.38 (11760 hom., cov: 32)
• Consequence: BLOC1S5-TXNDC5 ENST00000439343.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430
• Publications: 8 publications found

Genes affected

BLOC1S5-TXNDC5 (HGNC:42001): (BLOC1S5-TXNDC5 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring MUTED (muted homolog) and TXNDC5 (thioredoxin domain containing 5) genes on chromosome 6. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD) and is unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLOC1S5-TXNDC5	NR_037616.1	n.422+51341A>C		intron_variant	Intron 4 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLOC1S5-TXNDC5	ENST00000439343.2	n.372+51341A>C		intron_variant	Intron 4 of 12	2		ENSP00000454697.1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58486 AN: 151884 Hom.: 11765 Cov.: 32

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.401

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

GnomAD4 genome AF: 0.385 AC: 58495 AN: 152002 Hom.: 11760 Cov.: 32 AF XY: 0.384 AC XY: 28534 AN XY: 74288

African (AFR) AF: 0.485 AC: 20091 AN: 41438

American (AMR) AF: 0.294 AC: 4486 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1406 AN: 3472

East Asian (EAS) AF: 0.175 AC: 904 AN: 5180

South Asian (SAS) AF: 0.449 AC: 2158 AN: 4810

European-Finnish (FIN) AF: 0.334 AC: 3524 AN: 10560

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24571 AN: 67968

Other (OTH) AF: 0.398 AC: 839 AN: 2108

Alfa AF: 0.368 Hom.: 14929

Bravo AF: 0.384

Asia WGS AF: 0.315 AC: 1093 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.7
DANN	Benign	0.52
PhyloP100		-0.043
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: rs6597292; hg19: chr6-7975259;