rs1043784

chr6-7881698-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001718.6(BMP6):c.*1355T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,026 control chromosomes in the GnomAD database, including 4,871 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 0.21 (4871 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BMP6 NM_001718.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

Genes affected

BMP6 (HGNC:1073): (bone morphogenetic protein 6) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein regulates a wide range of biological processes including iron homeostasis, fat and bone development, and ovulation. Differential expression of this gene may be associated with progression of breast and prostate cancer. Mutations in this gene may be associated with iron overload in human patients. [provided by RefSeq, Jul 2016]

TXNDC5 (HGNC:21073): (thioredoxin domain containing 5) This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The encoded protein has an N-terminal endoplasmic reticulum (ER)-signal sequence, three catalytically active thioredoxin domains and a C-terminal ER-retention sequence. Its expression is induced by hypoxia and its role may be to protect hypoxic cells from apoptosis. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring upstream BLOC1S5 gene. [provided by RefSeq, Dec 2016]

BLOC1S5-TXNDC5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP6	NM_001718.6	c.*1355T>C		3_prime_UTR_variant	7/7	ENST00000283147.7
TXNDC5	NM_030810.5	c.*1446A>G		3_prime_UTR_variant	10/10	ENST00000379757.9
BLOC1S5-TXNDC5	NR_037616.1	n.2904A>G		non_coding_transcript_exon_variant	13/13
TXNDC5	NM_001145549.4	c.*1446A>G		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP6	ENST00000283147.7	c.*1355T>C		3_prime_UTR_variant	7/7	1	NM_001718.6	P1
TXNDC5	ENST00000379757.9	c.*1446A>G		3_prime_UTR_variant	10/10	1	NM_030810.5	P1
TXNDC5	ENST00000460138.5	n.2523A>G		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31732 AN: 151908 Hom.: 4850 Cov.: 32

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.177

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 EAS exome AF: 0.00

GnomAD4 genome AF: 0.209 AC: 31803 AN: 152026 Hom.: 4871 Cov.: 32 AF XY: 0.209 AC XY: 15533 AN XY: 74314

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.0965

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.179

Alfa AF: 0.133 Hom.: 1702

Bravo AF: 0.219

Asia WGS AF: 0.157 AC: 547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.85
Dann	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs1043784; hg19: chr6-7881931;