6-8010464-T-G

Variant names:

• chr6-8010464-T-G
• rs1002308
• ENST00000439343.2:n.372+15903A>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+15903A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 151,864 control chromosomes in the GnomAD database, including 15,980 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 0.44 (15980 hom., cov: 31)
• Consequence: BLOC1S5-TXNDC5 ENST00000439343.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691
• Publications: 5 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 (EAS) allele frequency at 95% confidence interval = 0.764 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.422+15903A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLOC1S5-TXNDC5	ENST00000439343.2	TSL:2	n.372+15903A>C		intron	N/A	ENSP00000454697.1

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67386 AN: 151746 Hom.: 15966 Cov.: 31

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.444 AC: 67437 AN: 151864 Hom.: 15980 Cov.: 31 AF XY: 0.450 AC XY: 33407 AN XY: 74222

African (AFR) AF: 0.305 AC: 12626 AN: 41412

American (AMR) AF: 0.502 AC: 7675 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1552 AN: 3472

East Asian (EAS) AF: 0.784 AC: 4053 AN: 5168

South Asian (SAS) AF: 0.434 AC: 2083 AN: 4802

European-Finnish (FIN) AF: 0.540 AC: 5677 AN: 10516

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.476 AC: 32302 AN: 67910

Other (OTH) AF: 0.422 AC: 889 AN: 2108

Alfa AF: 0.465 Hom.: 33920

Bravo AF: 0.439

Asia WGS AF: 0.597 AC: 2078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.79
PhyloP100		-0.69
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: rs1002308; hg19: chr6-8010697;