chr6-7881972-G-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000439343.2(BLOC1S5-TXNDC5):​n.*2169C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,584 control chromosomes in the GnomAD database, including 4,809 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 ( 4805 hom., cov: 32)
Exomes 𝑓: 0.15 ( 4 hom. )

Consequence

BLOC1S5-TXNDC5
ENST00000439343.2 non_coding_transcript_exon

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.133

Publications

17 publications found
Variant links:
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]
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]
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]
BMP6 Gene-Disease associations (from GenCC):
  • hemochromatosis type 5
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TXNDC5NM_030810.5 linkc.*1172C>T 3_prime_UTR_variant Exon 10 of 10 ENST00000379757.9 NP_110437.2 Q8NBS9-1
BLOC1S5-TXNDC5NR_037616.1 linkn.2630C>T non_coding_transcript_exon_variant Exon 13 of 13
TXNDC5NM_001145549.4 linkc.*1172C>T 3_prime_UTR_variant Exon 10 of 10 NP_001139021.1 Q8NBS9-2A0A024QZV0
BMP6NM_001718.6 linkc.*1629G>A downstream_gene_variant ENST00000283147.7 NP_001709.1 P22004Q4VBA3B4DUF7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BLOC1S5-TXNDC5ENST00000439343.2 linkn.*2169C>T non_coding_transcript_exon_variant Exon 13 of 13 2 ENSP00000454697.1 H3BN57
TXNDC5ENST00000379757.9 linkc.*1172C>T 3_prime_UTR_variant Exon 10 of 10 1 NM_030810.5 ENSP00000369081.4 Q8NBS9-1
BLOC1S5-TXNDC5ENST00000439343.2 linkn.*2169C>T 3_prime_UTR_variant Exon 13 of 13 2 ENSP00000454697.1 H3BN57
BMP6ENST00000283147.7 linkc.*1629G>A downstream_gene_variant 1 NM_001718.6 ENSP00000283147.6 P22004

Frequencies

GnomAD3 genomes
AF:
0.208
AC:
31576
AN:
152022
Hom.:
4785
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.435
Gnomad AMI
AF:
0.0746
Gnomad AMR
AF:
0.143
Gnomad ASJ
AF:
0.0965
Gnomad EAS
AF:
0.113
Gnomad SAS
AF:
0.112
Gnomad FIN
AF:
0.172
Gnomad MID
AF:
0.152
Gnomad NFE
AF:
0.113
Gnomad OTH
AF:
0.177
GnomAD4 exome
AF:
0.149
AC:
66
AN:
444
Hom.:
4
Cov.:
0
AF XY:
0.159
AC XY:
43
AN XY:
270
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
2
American (AMR)
AC:
0
AN:
0
Ashkenazi Jewish (ASJ)
AC:
0
AN:
0
East Asian (EAS)
AC:
0
AN:
0
South Asian (SAS)
AC:
0
AN:
0
European-Finnish (FIN)
AF:
0.146
AC:
62
AN:
426
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AF:
0.200
AC:
2
AN:
10
Other (OTH)
AF:
0.333
AC:
2
AN:
6
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.485
Heterozygous variant carriers
0
3
6
8
11
14
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.208
AC:
31645
AN:
152140
Hom.:
4805
Cov.:
32
AF XY:
0.208
AC XY:
15463
AN XY:
74392
show subpopulations
African (AFR)
AF:
0.435
AC:
18022
AN:
41438
American (AMR)
AF:
0.143
AC:
2180
AN:
15296
Ashkenazi Jewish (ASJ)
AF:
0.0965
AC:
335
AN:
3470
East Asian (EAS)
AF:
0.113
AC:
585
AN:
5186
South Asian (SAS)
AF:
0.112
AC:
542
AN:
4830
European-Finnish (FIN)
AF:
0.172
AC:
1822
AN:
10598
Middle Eastern (MID)
AF:
0.167
AC:
49
AN:
294
European-Non Finnish (NFE)
AF:
0.113
AC:
7665
AN:
68004
Other (OTH)
AF:
0.179
AC:
377
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1142
2284
3426
4568
5710
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
308
616
924
1232
1540
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.162
Hom.:
669
Bravo
AF:
0.218
Asia WGS
AF:
0.155
AC:
540
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
1.3
DANN
Benign
0.70
PhyloP100
-0.13
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
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

Publications

Other links and lift over

dbSNP: rs7764128; hg19: chr6-7882205; API