Genetic Variant ENST00000439343.2:n.372+38717C>G (chr6-7987650-G-C) – 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.372+38717C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 948,782 control chromosomes in the GnomAD database, including 48,777 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 0.38 ( 12417 hom., cov: 31)

Exomes 𝑓: 0.29 ( 36360 hom. )

Consequence

BLOC1S5-TXNDC5
ENST00000439343.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.85

Publications

10 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:

PIP5K1P1 (HGNC:28372): (phosphatidylinositol-4-phosphate 5-kinase type 1 pseudogene 1)

PIP5K1P1 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=-0.47).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP5K1P1	NR_027712.1 link	n.1549G>C		non_coding_transcript_exon_variant	Exon 1 of 1
BLOC1S5-TXNDC5	NR_037616.1 link	n.422+38717C>G		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.372+38717C>G		intron_variant	Intron 4 of 12	2		ENSP00000454697.1
PIP5K1P1	ENST00000460661.1 link	n.1114G>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

AF:

0.381

AC:

57888

AN:

151920

Hom.:

12400

Cov.:

show subpopulations

Gnomad AFR

AF:

0.570

Gnomad AMI

AF:

0.529

Gnomad AMR

AF:

0.348

Gnomad ASJ

AF:

0.376

Gnomad EAS

AF:

0.112

Gnomad SAS

AF:

0.254

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.318

Gnomad OTH

AF:

0.399

GnomAD2 exomes

AF:

0.309

AC:

77594

AN:

250994

AF XY:

0.305

show subpopulations

Gnomad AFR exome

AF:

0.579

Gnomad AMR exome

AF:

0.315

Gnomad ASJ exome

AF:

0.363

Gnomad EAS exome

AF:

0.120

Gnomad FIN exome

AF:

0.267

Gnomad NFE exome

AF:

0.316

Gnomad OTH exome

AF:

0.320

GnomAD4 exome

AF:

0.291

AC:

231831

AN:

796746

Hom.:

36360

Cov.:

AF XY:

0.292

AC XY:

123107

AN XY:

422200

show subpopulations

African (AFR)

AF:

0.559

AC:

11238

AN:

20104

American (AMR)

AF:

0.319

AC:

13925

AN:

43676

Ashkenazi Jewish (ASJ)

AF:

0.358

AC:

7817

AN:

21834

East Asian (EAS)

AF:

0.105

AC:

3842

AN:

36758

South Asian (SAS)

AF:

0.258

AC:

18895

AN:

73132

European-Finnish (FIN)

AF:

0.262

AC:

13723

AN:

52470

Middle Eastern (MID)

AF:

0.449

AC:

2004

AN:

4460

European-Non Finnish (NFE)

AF:

0.293

AC:

148272

AN:

506100

Other (OTH)

AF:

0.317

AC:

12115

AN:

38212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

9857

19714

29572

39429

49286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2430

4860

7290

9720

12150

<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:

0.381

AC:

57956

AN:

152036

Hom.:

12417

Cov.:

AF XY:

0.375

AC XY:

27905

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.570

AC:

23635

AN:

41448

American (AMR)

AF:

0.348

AC:

5314

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.376

AC:

1305

AN:

3470

East Asian (EAS)

AF:

0.112

AC:

581

AN:

5170

South Asian (SAS)

AF:

0.254

AC:

1223

AN:

4816

European-Finnish (FIN)

AF:

0.265

AC:

2803

AN:

10562

Middle Eastern (MID)

AF:

0.493

AC:

145

AN:

294

European-Non Finnish (NFE)

AF:

0.318

AC:

21624

AN:

67972

Other (OTH)

AF:

0.400

AC:

844

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1710

3420

5130

6840

8550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<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:

0.262

Hom.:

949

Bravo

AF:

0.399

Asia WGS

AF:

0.201

AC:

702

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

7.1

(source)

DANN

Benign

0.81

PhyloP100

1.9

Mutation Taster

=97/3

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