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GeneBe

rs41302895

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001718.6(BMP6):c.*1178A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0533 in 151,032 control chromosomes in the GnomAD database, including 310 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 0.053 ( 307 hom., cov: 33)
Exomes 𝑓: 0.15 ( 3 hom. )

Consequence

BMP6
NM_001718.6 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.34
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0722 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BMP6NM_001718.6 linkuse as main transcriptc.*1178A>T 3_prime_UTR_variant 7/7 ENST00000283147.7
TXNDC5NM_030810.5 linkuse as main transcriptc.*1623T>A 3_prime_UTR_variant 10/10 ENST00000379757.9
BLOC1S5-TXNDC5NR_037616.1 linkuse as main transcriptn.3081T>A non_coding_transcript_exon_variant 13/13
TXNDC5NM_001145549.4 linkuse as main transcriptc.*1623T>A 3_prime_UTR_variant 10/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BMP6ENST00000283147.7 linkuse as main transcriptc.*1178A>T 3_prime_UTR_variant 7/71 NM_001718.6 P1
TXNDC5ENST00000379757.9 linkuse as main transcriptc.*1623T>A 3_prime_UTR_variant 10/101 NM_030810.5 P1Q8NBS9-1
TXNDC5ENST00000460138.5 linkuse as main transcriptn.2700T>A non_coding_transcript_exon_variant 4/42

Frequencies

GnomAD3 genomes
AF:
0.0531
AC:
7997
AN:
150614
Hom.:
306
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0134
Gnomad AMI
AF:
0.228
Gnomad AMR
AF:
0.0321
Gnomad ASJ
AF:
0.0486
Gnomad EAS
AF:
0.000836
Gnomad SAS
AF:
0.0654
Gnomad FIN
AF:
0.113
Gnomad MID
AF:
0.0159
Gnomad NFE
AF:
0.0739
Gnomad OTH
AF:
0.0364
GnomAD4 exome
AF:
0.151
AC:
47
AN:
312
Hom.:
3
Cov.:
0
AF XY:
0.154
AC XY:
29
AN XY:
188
show subpopulations
Gnomad4 FIN exome
AF:
0.148
Gnomad4 OTH exome
AF:
0.500
GnomAD4 genome
AF:
0.0531
AC:
7999
AN:
150720
Hom.:
307
Cov.:
33
AF XY:
0.0538
AC XY:
3962
AN XY:
73636
show subpopulations
Gnomad4 AFR
AF:
0.0134
Gnomad4 AMR
AF:
0.0322
Gnomad4 ASJ
AF:
0.0486
Gnomad4 EAS
AF:
0.000839
Gnomad4 SAS
AF:
0.0654
Gnomad4 FIN
AF:
0.113
Gnomad4 NFE
AF:
0.0739
Gnomad4 OTH
AF:
0.0361
Alfa
AF:
0.0635
Hom.:
41
Bravo
AF:
0.0445

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
Cadd
Benign
0.087
Dann
Benign
0.52

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs41302895; hg19: chr6-7881754; COSMIC: COSV51663475; COSMIC: COSV51663475; API