Genetic Variant NM_000386.4:c.603C>G (chr17-30285430-G-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_000386.4(BLMH):c.603C>G(p.Thr201Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 1,609,002 control chromosomes in the GnomAD database, including 82,324 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 ( 7272 hom., cov: 32)

Exomes 𝑓: 0.32 ( 75052 hom. )

Consequence

BLMH
NM_000386.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.371

Publications

18 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP7

Synonymous conserved (PhyloP=0.371 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLMH	NM_000386.4 link	c.603C>G	p.Thr201Thr	synonymous_variant	Exon 6 of 12	ENST00000261714.11	NP_000377.1	Q13867

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLMH	ENST00000261714.11 link	c.603C>G	p.Thr201Thr	synonymous_variant	Exon 6 of 12	1	NM_000386.4	ENSP00000261714.6		Q13867

Frequencies

GnomAD3 genomes

AF:

0.303

AC:

46031

AN:

151820

Hom.:

7254

Cov.:

show subpopulations

Gnomad AFR

AF:

0.259

Gnomad AMI

AF:

0.431

Gnomad AMR

AF:

0.337

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.171

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.332

Gnomad OTH

AF:

0.300

GnomAD2 exomes

AF:

0.304

AC:

75567

AN:

248442

AF XY:

0.301

show subpopulations

Gnomad AFR exome

AF:

0.258

Gnomad AMR exome

AF:

0.347

Gnomad ASJ exome

AF:

0.243

Gnomad EAS exome

AF:

0.172

Gnomad FIN exome

AF:

0.344

Gnomad NFE exome

AF:

0.329

Gnomad OTH exome

AF:

0.308

GnomAD4 exome

AF:

0.318

AC:

463174

AN:

1457064

Hom.:

75052

Cov.:

AF XY:

0.316

AC XY:

228736

AN XY:

724820

show subpopulations

African (AFR)

AF:

0.254

AC:

8450

AN:

33252

American (AMR)

AF:

0.350

AC:

15433

AN:

44090

Ashkenazi Jewish (ASJ)

AF:

0.248

AC:

6453

AN:

26060

East Asian (EAS)

AF:

0.176

AC:

6977

AN:

39552

South Asian (SAS)

AF:

0.263

AC:

22458

AN:

85438

European-Finnish (FIN)

AF:

0.341

AC:

18201

AN:

53340

Middle Eastern (MID)

AF:

0.307

AC:

1765

AN:

5754

European-Non Finnish (NFE)

AF:

0.329

AC:

364760

AN:

1109370

Other (OTH)

AF:

0.310

AC:

18677

AN:

60208

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

15284

30569

45853

61138

76422

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11746

23492

35238

46984

58730

<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:

0.303

AC:

46091

AN:

151938

Hom.:

7272

Cov.:

AF XY:

0.300

AC XY:

22318

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.259

AC:

10729

AN:

41428

American (AMR)

AF:

0.338

AC:

5161

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

835

AN:

3466

East Asian (EAS)

AF:

0.170

AC:

880

AN:

5170

South Asian (SAS)

AF:

0.266

AC:

1278

AN:

4810

European-Finnish (FIN)

AF:

0.337

AC:

3546

AN:

10528

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.332

AC:

22533

AN:

67952

Other (OTH)

AF:

0.306

AC:

646

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1612

3224

4835

6447

8059

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:

0.319

Hom.:

2632

Bravo

AF:

0.300

Asia WGS

AF:

0.285

AC:

990

AN:

3478

EpiCase

AF:

0.325

EpiControl

AF:

0.317

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

1.0

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