17-30249058-T-C

Variant names:

• chr17-30249058-T-C
• rs1050565
• NM_000386.4:c.1327A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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. 15/21 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
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.19
• Publications: 70 publications found

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]

ENSG00000266120 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000386.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLMH	NM_000386.4	MANE Select	c.1327A>G	p.Ile443Val	missense	Exon 12 of 12	NP_000377.1	Q13867

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLMH	ENST00000261714.11	TSL:1 MANE Select	c.1327A>G	p.Ile443Val	missense	Exon 12 of 12	ENSP00000261714.6	Q13867
	BLMH	ENST00000935069.1		c.1420A>G	p.Ile474Val	missense	Exon 13 of 13	ENSP00000605128.1
	BLMH	ENST00000935072.1		c.1207A>G	p.Ile403Val	missense	Exon 11 of 11	ENSP00000605131.1

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

GnomAD2 exomes AF: 0.303 AC: 76102 AN: 251188 AF XY: 0.300

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 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

African (AFR) AF: 0.207 AC: 6935 AN: 33468

American (AMR) AF: 0.351 AC: 15680 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 6397 AN: 26132

East Asian (EAS) AF: 0.176 AC: 6980 AN: 39696

South Asian (SAS) AF: 0.266 AC: 22924 AN: 86250

European-Finnish (FIN) AF: 0.342 AC: 18251 AN: 53420

Middle Eastern (MID) AF: 0.305 AC: 1758 AN: 5764

European-Non Finnish (NFE) AF: 0.329 AC: 366003 AN: 1111788

Other (OTH) AF: 0.306 AC: 18509 AN: 60392

GnomAD4 genome AF: 0.290 AC: 44033 AN: 152052 Hom.: 6785 Cov.: 31 AF XY: 0.287 AC XY: 21299 AN XY: 74324

African (AFR) AF: 0.212 AC: 8791 AN: 41500

American (AMR) AF: 0.334 AC: 5097 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 825 AN: 3472

East Asian (EAS) AF: 0.165 AC: 853 AN: 5164

South Asian (SAS) AF: 0.266 AC: 1282 AN: 4814

European-Finnish (FIN) AF: 0.336 AC: 3558 AN: 10574

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22516 AN: 67946

Other (OTH) AF: 0.298 AC: 630 AN: 2114

Alfa AF: 0.312 Hom.: 36091

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Alzheimer disease type 1 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		1.2
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
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

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