17-30254002-G-C

Variant names:

• chr17-30254002-G-C
• rs1552472
• NM_000386.4:c.1217-4834C>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.1217-4834C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0841 in 152,166 control chromosomes in the GnomAD database, including 832 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 0.084 (832 hom., cov: 32)
• Consequence: BLMH NM_000386.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20
• Publications: 0 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=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 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.1217-4834C>G		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.1217-4834C>G		intron	N/A	ENSP00000261714.6
	ENSG00000266120	ENST00000577420.2	TSL:3	n.428+1760G>C		intron	N/A
	BLMH	ENST00000578090.5	TSL:2	n.*891-4834C>G		intron	N/A	ENSP00000462353.1

Frequencies

GnomAD3 genomes AF: 0.0841 AC: 12785 AN: 152046 Hom.: 831 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0528

Gnomad ASJ AF: 0.0841

Gnomad EAS AF: 0.0454

Gnomad SAS AF: 0.0964

Gnomad FIN AF: 0.0442

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.0489

Gnomad OTH AF: 0.0829

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

GnomAD4 genome AF: 0.0841 AC: 12803 AN: 152166 Hom.: 832 Cov.: 32 AF XY: 0.0831 AC XY: 6179 AN XY: 74390

African (AFR) AF: 0.169 AC: 7020 AN: 41504

American (AMR) AF: 0.0526 AC: 804 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0841 AC: 292 AN: 3470

East Asian (EAS) AF: 0.0445 AC: 231 AN: 5186

South Asian (SAS) AF: 0.0959 AC: 462 AN: 4818

European-Finnish (FIN) AF: 0.0442 AC: 468 AN: 10592

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0489 AC: 3323 AN: 67986

Other (OTH) AF: 0.0820 AC: 173 AN: 2110

Alfa AF: 0.0700 Hom.: 62

Bravo AF: 0.0871

Asia WGS AF: 0.0800 AC: 277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.89
PhyloP100		2.2
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: rs1552472; hg19: chr17-28581020;