rs1050565

chr17-30249058-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.29 (6785 hom., cov: 31)
  • Exomes 𝑓: 0.32 (74895 hom.)
• Consequence: BLMH NM_000386.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.19

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 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 no_assertion_criteria_provided, 0 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	UniProt
BLMH	NM_000386.4	c.1327A>G	p.Ile443Val	missense_variant	12/12	ENST00000261714.11
LOC105371720	XR_001752824.2	n.892-729T>C		intron_variant, non_coding_transcript_variant
LOC105371720	XR_007065695.1	n.756-729T>C		intron_variant, non_coding_transcript_variant
LOC105371720	XR_007065698.1	n.756-3016T>C		intron_variant, non_coding_transcript_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.290 AC: 43985 AN: 151934 Hom.: 6767 Cov.: 31

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

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.: 38 AF XY: 0.315 AC XY: 229085 AN XY: 727122

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.: 31 AF XY: 0.287 AC XY: 21299 AN XY: 74324

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:1

Revision: no assertion criteria provided

Submissions by phenotype

BLEOMYCIN HYDROLASE POLYMORPHISM Benign:1

Benign, no assertion criteria provided

literature only

OMIM

May 28, 1996

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	3.5
Dann	Benign	0.66
DEOGEN2	Benign	0.095	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-2.3	N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.80	N
REVEL	Benign	0.031
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.023
MPC		0.22
ClinPred		0.00030	T
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

Other links and lift over

dbSNP: rs1050565; hg19: chr17-28576076; COSMIC: COSV55584216; COSMIC: COSV55584216;