ENST00000439343.2:n.373-6746A>C

Variant names:

• chr6-7911469-T-G
• rs3812162
• ENST00000439343.2:n.373-6746A>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.373-6746A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 152,030 control chromosomes in the GnomAD database, including 14,500 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 0.42 (14500 hom., cov: 32)
• Consequence: BLOC1S5-TXNDC5 ENST00000439343.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 13 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLOC1S5-TXNDC5	NR_037616.1	n.423-6746A>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.373-6746A>C		intron_variant	Intron 4 of 12	2		ENSP00000454697.1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63464 AN: 151912 Hom.: 14503 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.441

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

GnomAD4 genome AF: 0.417 AC: 63465 AN: 152030 Hom.: 14500 Cov.: 32 AF XY: 0.415 AC XY: 30812 AN XY: 74302

African (AFR) AF: 0.240 AC: 9974 AN: 41484

American (AMR) AF: 0.424 AC: 6473 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2038 AN: 3464

East Asian (EAS) AF: 0.205 AC: 1059 AN: 5156

South Asian (SAS) AF: 0.455 AC: 2190 AN: 4816

European-Finnish (FIN) AF: 0.492 AC: 5208 AN: 10578

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35078 AN: 67950

Other (OTH) AF: 0.436 AC: 918 AN: 2106

Alfa AF: 0.481 Hom.: 69008

Bravo AF: 0.402

Asia WGS AF: 0.316 AC: 1101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.68
PhyloP100		-1.3
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: rs3812162; hg19: chr6-7911702;