17-30263512-T-C

Position:

• chr17-30263512-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLMH	NM_000386.4	c.1216+3373A>G		intron_variant		ENST00000261714.11	NP_000377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLMH	ENST00000261714.11	c.1216+3373A>G		intron_variant		1	NM_000386.4	ENSP00000261714	P1
BLMH	ENST00000578090.5	c.*890+3373A>G		intron_variant, NMD_transcript_variant		2		ENSP00000462353

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

Gnomad4 AFR AF: 0.0205

Gnomad4 AMR AF: 0.0707

Gnomad4 ASJ AF: 0.0879

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0137

Gnomad4 FIN AF: 0.0946

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.0858

Alfa AF: 0.110 Hom.: 1447

Bravo AF: 0.0772

Asia WGS AF: 0.0140 AC: 48 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.17
DANN	Benign	0.49

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: rs2129785; hg19: chr17-28590530;