17-30277271-C-T

Variant names:

• chr17-30277271-C-T
• rs8072345
• NM_000386.4:c.646-3074G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000386.4(BLMH):​c.646-3074G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 151,994 control chromosomes in the GnomAD database, including 23,504 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 0.53 (23504 hom., cov: 32)
• Consequence: BLMH NM_000386.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.448
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLMH	NM_000386.4	c.646-3074G>A		intron_variant	Intron 6 of 11	ENST00000261714.11	NP_000377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLMH	ENST00000261714.11	c.646-3074G>A		intron_variant	Intron 6 of 11	1	NM_000386.4	ENSP00000261714.6

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80783 AN: 151876 Hom.: 23444 Cov.: 32

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.488

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.532 AC: 80908 AN: 151994 Hom.: 23504 Cov.: 32 AF XY: 0.528 AC XY: 39206 AN XY: 74282

African (AFR) AF: 0.772 AC: 32039 AN: 41506

American (AMR) AF: 0.468 AC: 7141 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1352 AN: 3464

East Asian (EAS) AF: 0.215 AC: 1112 AN: 5172

South Asian (SAS) AF: 0.395 AC: 1903 AN: 4818

European-Finnish (FIN) AF: 0.493 AC: 5194 AN: 10534

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30534 AN: 67928

Other (OTH) AF: 0.492 AC: 1038 AN: 2110

Alfa AF: 0.439 Hom.: 3583

Bravo AF: 0.536

Asia WGS AF: 0.402 AC: 1398 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.74
PhyloP100		-0.45
Mutation Taster		=100/0	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: rs8072345; hg19: chr17-28604289;