6-7936242-C-T

Variant names:

• chr6-7936242-C-T
• rs627957
• ENST00000439343.2:n.373-31519G>A

Variant summary

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

The ENST00000439343.2(BLOC1S5-TXNDC5):​n.373-31519G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 152,056 control chromosomes in the GnomAD database, including 32,636 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 0.63 (32636 hom., cov: 33)
• Consequence: BLOC1S5-TXNDC5 ENST00000439343.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000439343.2. 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
	BLOC1S5-TXNDC5	NR_037616.1		n.423-31519G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLOC1S5-TXNDC5	ENST00000439343.2	TSL:2	n.373-31519G>A		intron	N/A	ENSP00000454697.1	H3BN57

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96480 AN: 151940 Hom.: 32609 Cov.: 33

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.704

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.635 AC: 96538 AN: 152056 Hom.: 32636 Cov.: 33 AF XY: 0.633 AC XY: 47050 AN XY: 74344

African (AFR) AF: 0.385 AC: 15963 AN: 41472

American (AMR) AF: 0.695 AC: 10618 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2706 AN: 3464

East Asian (EAS) AF: 0.721 AC: 3727 AN: 5170

South Asian (SAS) AF: 0.567 AC: 2736 AN: 4826

European-Finnish (FIN) AF: 0.740 AC: 7795 AN: 10530

Middle Eastern (MID) AF: 0.705 AC: 206 AN: 292

European-Non Finnish (NFE) AF: 0.746 AC: 50727 AN: 67996

Other (OTH) AF: 0.672 AC: 1419 AN: 2112

Alfa AF: 0.647 Hom.: 6532

Bravo AF: 0.625

Asia WGS AF: 0.627 AC: 2175 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.33
DANN	Benign	0.59
PhyloP100		-1.1
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: rs627957;

hg19: chr6-7936475;