rs1050565

Positions:

chr17-30249058-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000386.4(BLMH):c.1327A>G(p.Ile443Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 1,613,660 control chromosomes in the GnomAD database, including 81,680 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.29 ( 6785 hom., cov: 31)

Exomes 𝑓: 0.32 ( 74895 hom. )

Consequence

BLMH
NM_000386.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.19

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004819095).

BP6

Variant 17-30249058-T-C is Benign according to our data. Variant chr17-30249058-T-C is described in ClinVar as [Benign]. Clinvar id is 7248.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
BLMH	NM_000386.4 linkuse as main transcript	c.1327A>G	p.Ile443Val	missense_variant	12/12	ENST00000261714.11	NP_000377.1
LOC105371720	XR_001752824.2 linkuse as main transcript	n.892-729T>C		intron_variant, non_coding_transcript_variant
LOC105371720	XR_007065695.1 linkuse as main transcript	n.756-729T>C		intron_variant, non_coding_transcript_variant
LOC105371720	XR_007065698.1 linkuse as main transcript	n.756-3016T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
BLMH	ENST00000261714.11 linkuse as main transcript	c.1327A>G	p.Ile443Val	missense_variant	12/12	1	NM_000386.4	ENSP00000261714	P1
	ENST00000577420.1 linkuse as main transcript	n.61-3016T>C		intron_variant, non_coding_transcript_variant		3
BLMH	ENST00000578795.1 linkuse as main transcript	n.1226A>G		non_coding_transcript_exon_variant	1/1
BLMH	ENST00000578090.5 linkuse as main transcript	c.*1001A>G		3_prime_UTR_variant, NMD_transcript_variant	11/11	2		ENSP00000462353

Frequencies

GnomAD3 genomes

AF:

0.290

AC:

43985

AN:

151934

Hom.:

6767

Cov.:

show subpopulations

Gnomad AFR

AF:

0.212

Gnomad AMI

AF:

0.430

Gnomad AMR

AF:

0.333

Gnomad ASJ

AF:

0.238

Gnomad EAS

AF:

0.166

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.336

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.292

GnomAD3 exomes

AF:

0.303

AC:

76102

AN:

251188

Hom.:

12113

AF XY:

0.300

AC XY:

40786

AN XY:

135732

show subpopulations

Gnomad AFR exome

AF:

0.212

Gnomad AMR exome

AF:

0.351

Gnomad ASJ exome

AF:

0.239

Gnomad EAS exome

AF:

0.171

Gnomad SAS exome

AF:

0.265

Gnomad FIN exome

AF:

0.345

Gnomad NFE exome

AF:

0.330

Gnomad OTH exome

AF:

0.312

GnomAD4 exome

AF:

0.317

AC:

463437

AN:

1461608

Hom.:

74895

Cov.:

AF XY:

0.315

AC XY:

229085

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.207

Gnomad4 AMR exome

AF:

0.351

Gnomad4 ASJ exome

AF:

0.245

Gnomad4 EAS exome

AF:

0.176

Gnomad4 SAS exome

AF:

0.266

Gnomad4 FIN exome

AF:

0.342

Gnomad4 NFE exome

AF:

0.329

Gnomad4 OTH exome

AF:

0.306

GnomAD4 genome

AF:

0.290

AC:

44033

AN:

152052

Hom.:

6785

Cov.:

AF XY:

0.287

AC XY:

21299

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.212

Gnomad4 AMR

AF:

0.334

Gnomad4 ASJ

AF:

0.238

Gnomad4 EAS

AF:

0.165

Gnomad4 SAS

AF:

0.266

Gnomad4 FIN

AF:

0.336

Gnomad4 NFE

AF:

0.331

Gnomad4 OTH

AF:

0.298

Alfa

AF:

0.315

Hom.:

20240

Bravo

AF:

0.285

TwinsUK

AF:

0.330

AC:

1225

ALSPAC

AF:

0.337

AC:

1298

ESP6500AA

AF:

0.214

AC:

941

ESP6500EA

AF:

0.322

AC:

2771

ExAC

AF:

0.300

AC:

36383

Asia WGS

AF:

0.280

AC:

974

AN:

3478

EpiCase

AF:

0.327

EpiControl

AF:

0.320

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

BLEOMYCIN HYDROLASE POLYMORPHISM

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

May 28, 1996

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

3.5

DANN

Benign

0.66

DEOGEN2

Benign

0.095

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.65

MetaRNN

Benign

0.0048

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-2.3

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.36

PROVEAN

Benign

0.80

REVEL

Benign

0.031

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.023

MPC

0.22

ClinPred

0.00030

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.023

gMVP

0.16

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over