Genetic Variant BLOC1S5-TXNDC5:n.373-33817C>T (chr6-7938540-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000439343.2(BLOC1S5-TXNDC5):n.373-33817C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 152,174 control chromosomes in the GnomAD database, including 46,785 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 0.78 ( 46763 hom., cov: 32)

Exomes 𝑓: 0.88 ( 22 hom. )

Consequence

BLOC1S5-TXNDC5
ENST00000439343.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.17

Publications

5 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]

BLOC1S5-TXNDC5 links:

ENSG00000217746 (HGNC:):

ENSG00000217746 links:

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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=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLOC1S5-TXNDC5	NR_037616.1 link	n.423-33817C>T		intron_variant	Intron 4 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLOC1S5-TXNDC5	ENST00000439343.2 link	n.373-33817C>T		intron_variant	Intron 4 of 12	2		ENSP00000454697.1		H3BN57
ENSG00000217746	ENST00000405326.1 link	n.783C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

AF:

0.778

AC:

118314

AN:

151998

Hom.:

46730

Cov.:

show subpopulations

Gnomad AFR

AF:

0.632

Gnomad AMI

AF:

0.891

Gnomad AMR

AF:

0.805

Gnomad ASJ

AF:

0.888

Gnomad EAS

AF:

0.802

Gnomad SAS

AF:

0.807

Gnomad FIN

AF:

0.854

Gnomad MID

AF:

0.883

Gnomad NFE

AF:

0.838

Gnomad OTH

AF:

0.799

GnomAD4 exome

AF:

0.879

AC:

AN:

Hom.:

Cov.:

AF XY:

0.886

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.750

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.880

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.778

AC:

118401

AN:

152116

Hom.:

46763

Cov.:

AF XY:

0.778

AC XY:

57873

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.632

AC:

26208

AN:

41466

American (AMR)

AF:

0.805

AC:

12298

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.888

AC:

3082

AN:

3470

East Asian (EAS)

AF:

0.802

AC:

4147

AN:

5174

South Asian (SAS)

AF:

0.807

AC:

3888

AN:

4816

European-Finnish (FIN)

AF:

0.854

AC:

9055

AN:

10606

Middle Eastern (MID)

AF:

0.888

AC:

261

AN:

294

European-Non Finnish (NFE)

AF:

0.838

AC:

56958

AN:

67980

Other (OTH)

AF:

0.801

AC:

1691

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1272

2544

3815

5087

6359

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

864

1728

2592

3456

4320

<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:

0.822

Hom.:

221812

Bravo

AF:

0.769

Asia WGS

AF:

0.799

AC:

2777

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.51

(source)

DANN

Benign

0.60

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over