rs1594467

Variant names:

• chr6-7920128-A-G
• rs1594467
• ENST00000439343.2:n.373-15405T>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.373-15405T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,138 control chromosomes in the GnomAD database, including 10,244 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 0.36 (10244 hom., cov: 33)
• Consequence: BLOC1S5-TXNDC5 ENST00000439343.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.445 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.423-15405T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLOC1S5-TXNDC5	ENST00000439343.2	TSL:2	n.373-15405T>C		intron	N/A	ENSP00000454697.1	H3BN57

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54657 AN: 152020 Hom.: 10229 Cov.: 33

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.0866

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.360 AC: 54707 AN: 152138 Hom.: 10244 Cov.: 33 AF XY: 0.360 AC XY: 26755 AN XY: 74364

African (AFR) AF: 0.450 AC: 18685 AN: 41486

American (AMR) AF: 0.289 AC: 4414 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1608 AN: 3468

East Asian (EAS) AF: 0.0860 AC: 446 AN: 5186

South Asian (SAS) AF: 0.415 AC: 2002 AN: 4820

European-Finnish (FIN) AF: 0.364 AC: 3847 AN: 10576

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22503 AN: 67986

Other (OTH) AF: 0.355 AC: 751 AN: 2116

Alfa AF: 0.344 Hom.: 25142

Bravo AF: 0.353

Asia WGS AF: 0.277 AC: 960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.12
DANN	Benign	0.46
PhyloP100		-2.5
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: rs1594467;

hg19: chr6-7920361;