chr6-7993744-C-T

Variant names:

• chr6-7993744-C-T
• rs2567226
• ENST00000439343.2:n.372+32623G>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.372+32623G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 151,940 control chromosomes in the GnomAD database, including 15,446 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 0.43 (15446 hom., cov: 31)
• Consequence: BLOC1S5-TXNDC5 ENST00000439343.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLOC1S5-TXNDC5	NR_037616.1		n.422+32623G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLOC1S5-TXNDC5	ENST00000439343.2	TSL:2	n.372+32623G>A		intron	N/A	ENSP00000454697.1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65891 AN: 151822 Hom.: 15445 Cov.: 31

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.394

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.434 AC: 65930 AN: 151940 Hom.: 15446 Cov.: 31 AF XY: 0.441 AC XY: 32745 AN XY: 74258

African (AFR) AF: 0.279 AC: 11540 AN: 41422

American (AMR) AF: 0.461 AC: 7040 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1678 AN: 3470

East Asian (EAS) AF: 0.756 AC: 3899 AN: 5160

South Asian (SAS) AF: 0.606 AC: 2912 AN: 4804

European-Finnish (FIN) AF: 0.526 AC: 5556 AN: 10562

Middle Eastern (MID) AF: 0.397 AC: 116 AN: 292

European-Non Finnish (NFE) AF: 0.471 AC: 32011 AN: 67926

Other (OTH) AF: 0.424 AC: 896 AN: 2112

Alfa AF: 0.442 Hom.: 2449

Bravo AF: 0.419

Asia WGS AF: 0.670 AC: 2329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.031
DANN	Benign	0.39
PhyloP100		-1.7
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: rs2567226; hg19: chr6-7993977;