rs12204273

Variant names:

• chr6-8002472-A-G
• rs12204273
• ENST00000439343.2:n.372+23895T>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+23895T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,092 control chromosomes in the GnomAD database, including 2,936 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 0.19 (2936 hom., cov: 32)
• Consequence: BLOC1S5-TXNDC5 ENST00000439343.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.361
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 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+23895T>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+23895T>C		intron	N/A	ENSP00000454697.1	H3BN57

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28668 AN: 151976 Hom.: 2934 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.0937

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.0821

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.189 AC: 28683 AN: 152092 Hom.: 2936 Cov.: 32 AF XY: 0.186 AC XY: 13810 AN XY: 74338

African (AFR) AF: 0.258 AC: 10688 AN: 41460

American (AMR) AF: 0.187 AC: 2864 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0937 AC: 325 AN: 3470

East Asian (EAS) AF: 0.143 AC: 739 AN: 5168

South Asian (SAS) AF: 0.0818 AC: 394 AN: 4818

European-Finnish (FIN) AF: 0.178 AC: 1879 AN: 10572

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11325 AN: 67986

Other (OTH) AF: 0.175 AC: 371 AN: 2114

Alfa AF: 0.170 Hom.: 3101

Bravo AF: 0.194

Asia WGS AF: 0.134 AC: 464 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	2.0
DANN	Benign	0.83
PhyloP100		-0.36
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: rs12204273;

hg19: chr6-8002705;