NM_000386.4:c.1217-3134G>A

Variant names:

• chr17-30252302-C-T
• rs7223821
• NM_000386.4:c.1217-3134G>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.1217-3134G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,864 control chromosomes in the GnomAD database, including 7,301 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 0.30 (7301 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BLMH NM_000386.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.523
• 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]

ENSG00000266120 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.332 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLMH	NM_000386.4	MANE Select	c.1217-3134G>A		intron	N/A	NP_000377.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLMH	ENST00000261714.11	TSL:1 MANE Select	c.1217-3134G>A		intron	N/A	ENSP00000261714.6
	ENSG00000266120	ENST00000577420.2	TSL:3	n.428+60C>T		intron	N/A
	BLMH	ENST00000578090.5	TSL:2	n.*891-3134G>A		intron	N/A	ENSP00000462353.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46117 AN: 151746 Hom.: 7280 Cov.: 30

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.302

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.304 AC: 46182 AN: 151864 Hom.: 7301 Cov.: 30 AF XY: 0.301 AC XY: 22352 AN XY: 74224

African (AFR) AF: 0.261 AC: 10791 AN: 41398

American (AMR) AF: 0.340 AC: 5189 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 825 AN: 3466

East Asian (EAS) AF: 0.177 AC: 914 AN: 5166

South Asian (SAS) AF: 0.266 AC: 1280 AN: 4804

European-Finnish (FIN) AF: 0.337 AC: 3545 AN: 10534

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

European-Non Finnish (NFE) AF: 0.331 AC: 22507 AN: 67914

Other (OTH) AF: 0.307 AC: 648 AN: 2108

Alfa AF: 0.315 Hom.: 1291

Bravo AF: 0.301

Asia WGS AF: 0.287 AC: 998 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.6
DANN	Benign	0.84
PhyloP100		-0.52
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: rs7223821; hg19: chr17-28579320;