rs6923488

Variant names:

• chr6-7918172-C-T
• rs6923488
• ENST00000439343.2:n.373-13449G>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.373-13449G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,222 control chromosomes in the GnomAD database, including 5,322 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 0.26 (5322 hom., cov: 33)
• Consequence: BLOC1S5-TXNDC5 ENST00000439343.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.517
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.297 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.423-13449G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLOC1S5-TXNDC5	ENST00000439343.2	TSL:2	n.373-13449G>A		intron	N/A	ENSP00000454697.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39760 AN: 152104 Hom.: 5321 Cov.: 33

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.261 AC: 39776 AN: 152222 Hom.: 5322 Cov.: 33 AF XY: 0.256 AC XY: 19061 AN XY: 74430

African (AFR) AF: 0.237 AC: 9846 AN: 41530

American (AMR) AF: 0.224 AC: 3427 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 753 AN: 3472

East Asian (EAS) AF: 0.193 AC: 998 AN: 5184

South Asian (SAS) AF: 0.218 AC: 1053 AN: 4824

European-Finnish (FIN) AF: 0.230 AC: 2435 AN: 10594

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20414 AN: 68006

Other (OTH) AF: 0.258 AC: 545 AN: 2110

Alfa AF: 0.286 Hom.: 4794

Bravo AF: 0.261

Asia WGS AF: 0.212 AC: 739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.66
PhyloP100		-0.52
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: rs6923488; hg19: chr6-7918405;