rs7214014

Positions:

• chr17-30284376-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000386.4(BLMH):​c.645+1012C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 152,014 control chromosomes in the GnomAD database, including 23,938 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 0.54 (23938 hom., cov: 31)
• Consequence: BLMH NM_000386.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.220

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLMH	NM_000386.4	c.645+1012C>T		intron_variant		ENST00000261714.11	NP_000377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLMH	ENST00000261714.11	c.645+1012C>T		intron_variant		1	NM_000386.4	ENSP00000261714.6

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81327 AN: 151896 Hom.: 23874 Cov.: 31

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.536 AC: 81456 AN: 152014 Hom.: 23938 Cov.: 31 AF XY: 0.531 AC XY: 39455 AN XY: 74306

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.449

Gnomad4 OTH AF: 0.492

Alfa AF: 0.476 Hom.: 8788

Bravo AF: 0.541

Asia WGS AF: 0.403 AC: 1401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.39

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: rs7214014; hg19: chr17-28611394;