17-30263512-T-C

Variant names:

• chr17-30263512-T-C
• rs2129785
• NM_000386.4:c.1216+3373A>G

Variant summary

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

The NM_000386.4(BLMH):​c.1216+3373A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0812 in 152,180 control chromosomes in the GnomAD database, including 708 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 0.081 (708 hom., cov: 32)
• Consequence: BLMH NM_000386.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 9 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.126 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.1216+3373A>G		intron	N/A	NP_000377.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLMH	ENST00000261714.11	TSL:1 MANE Select	c.1216+3373A>G		intron	N/A	ENSP00000261714.6
	BLMH	ENST00000935069.1		c.1217-1748A>G		intron	N/A	ENSP00000605128.1
	BLMH	ENST00000935072.1		c.1096+7809A>G		intron	N/A	ENSP00000605131.1

Frequencies

GnomAD3 genomes AF: 0.0813 AC: 12358 AN: 152062 Hom.: 708 Cov.: 32

Gnomad AFR AF: 0.0206

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.0708

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.0946

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.0862

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

GnomAD4 genome AF: 0.0812 AC: 12360 AN: 152180 Hom.: 708 Cov.: 32 AF XY: 0.0783 AC XY: 5825 AN XY: 74394

African (AFR) AF: 0.0205 AC: 851 AN: 41510

American (AMR) AF: 0.0707 AC: 1082 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0879 AC: 305 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0137 AC: 66 AN: 4820

European-Finnish (FIN) AF: 0.0946 AC: 1001 AN: 10580

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8696 AN: 68006

Other (OTH) AF: 0.0858 AC: 181 AN: 2110

Alfa AF: 0.107 Hom.: 3461

Bravo AF: 0.0772

Asia WGS AF: 0.0140 AC: 48 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.17
DANN	Benign	0.49
PhyloP100		-1.4
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: rs2129785; hg19: chr17-28590530;