dbSNP rs7223821: BLMH:c.1217-3134G>A (chr17-30252302-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000386.4(BLMH):c.1217-3134G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,864 control chromosomes in the GnomAD database, including 7,301 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 0.30 ( 7301 hom., cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BLMH
NM_000386.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.523

Publications

4 publications found

Variant links:

Genes affected

BLMH (HGNC:1059): (bleomycin hydrolase) Bleomycin hydrolase (BMH) is a cytoplasmic cysteine peptidase that is highly conserved through evolution; however, the only known activity of the enzyme is metabolic inactivation of the glycopeptide bleomycin (BLM), an essential component of combination chemotherapy regimens for cancer. The protein contains the signature active site residues of the cysteine protease papain superfamily. [provided by RefSeq, Jul 2008]

BLMH links:

ENSG00000266120 (HGNC:):

ENSG00000266120 links:

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=-0.56).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLMH	NM_000386.4 link	c.1217-3134G>A		intron_variant	Intron 11 of 11	ENST00000261714.11	NP_000377.1
LOC105371720	XR_007065698.1 link	n.*69C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
BLMH	ENST00000261714.11 link	c.1217-3134G>A	intron_variant	Intron 11 of 11	1	NM_000386.4	ENSP00000261714.6
ENSG00000266120	ENST00000577420.2 link	n.428+60C>T	intron_variant	Intron 2 of 2	3
BLMH	ENST00000578090.5 link	n.*891-3134G>A	intron_variant	Intron 10 of 10	2		ENSP00000462353.1

Frequencies

GnomAD3 genomes

AF:

0.304

AC:

46117

AN:

151746

Hom.:

7280

Cov.:

show subpopulations

Gnomad AFR

AF:

0.261

Gnomad AMI

AF:

0.431

Gnomad AMR

AF:

0.339

Gnomad ASJ

AF:

0.238

Gnomad EAS

AF:

0.177

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.302

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.304

AC:

46182

AN:

151864

Hom.:

7301

Cov.:

AF XY:

0.301

AC XY:

22352

AN XY:

74224

show subpopulations

African (AFR)

AF:

0.261

AC:

10791

AN:

41398

American (AMR)

AF:

0.340

AC:

5189

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

825

AN:

3466

East Asian (EAS)

AF:

0.177

AC:

914

AN:

5166

South Asian (SAS)

AF:

0.266

AC:

1280

AN:

4804

European-Finnish (FIN)

AF:

0.337

AC:

3545

AN:

10534

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.331

AC:

22507

AN:

67914

Other (OTH)

AF:

0.307

AC:

648

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1607

3214

4822

6429

8036

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

460

920

1380

1840

2300

<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:

0.315

Hom.:

1291

Bravo

AF:

0.301

Asia WGS

AF:

0.287

AC:

998

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.6

(source)

DANN

Benign

0.84

PhyloP100

-0.52

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over