17-30285430-G-C

Position:

• chr17-30285430-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_000386.4(BLMH):​c.603C>G​(p.Thr201=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 1,609,002 control chromosomes in the GnomAD database, including 82,324 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 (7272 hom., cov: 32)
  • Exomes 𝑓: 0.32 (75052 hom.)
• Consequence: BLMH NM_000386.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.371

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=0.371 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLMH	NM_000386.4	c.603C>G	p.Thr201=	synonymous_variant	6/12	ENST00000261714.11	NP_000377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLMH	ENST00000261714.11	c.603C>G	p.Thr201=	synonymous_variant	6/12	1	NM_000386.4	ENSP00000261714	P1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46031 AN: 151820 Hom.: 7254 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.300

GnomAD3 exomes AF: 0.304 AC: 75567 AN: 248442 Hom.: 12085 AF XY: 0.301 AC XY: 40418 AN XY: 134354

Gnomad AFR exome AF: 0.258

Gnomad AMR exome AF: 0.347

Gnomad ASJ exome AF: 0.243

Gnomad EAS exome AF: 0.172

Gnomad SAS exome AF: 0.261

Gnomad FIN exome AF: 0.344

Gnomad NFE exome AF: 0.329

Gnomad OTH exome AF: 0.308

GnomAD4 exome AF: 0.318 AC: 463174 AN: 1457064 Hom.: 75052 Cov.: 33 AF XY: 0.316 AC XY: 228736 AN XY: 724820

Gnomad4 AFR exome AF: 0.254

Gnomad4 AMR exome AF: 0.350

Gnomad4 ASJ exome AF: 0.248

Gnomad4 EAS exome AF: 0.176

Gnomad4 SAS exome AF: 0.263

Gnomad4 FIN exome AF: 0.341

Gnomad4 NFE exome AF: 0.329

Gnomad4 OTH exome AF: 0.310

GnomAD4 genome AF: 0.303 AC: 46091 AN: 151938 Hom.: 7272 Cov.: 32 AF XY: 0.300 AC XY: 22318 AN XY: 74272

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.306

Alfa AF: 0.319 Hom.: 2632

Bravo AF: 0.300

Asia WGS AF: 0.285 AC: 990 AN: 3478

EpiCase AF: 0.325

EpiControl AF: 0.317

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	10
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs7342921; hg19: chr17-28612448; COSMIC: COSV55585518; COSMIC: COSV55585518;