rs7223821

Variant names:

• chr17-30252302-C-T
• rs7223821
• NM_000386.4:c.1217-3134G>A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLMH	NM_000386.4	c.1217-3134G>A		intron_variant	Intron 11 of 11	ENST00000261714.11	NP_000377.1
LOC105371720	XR_007065698.1	n.*69C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLMH	ENST00000261714.11	c.1217-3134G>A		intron_variant	Intron 11 of 11	1	NM_000386.4	ENSP00000261714.6
BLMH	ENST00000578090.5	n.*891-3134G>A		intron_variant	Intron 10 of 10	2		ENSP00000462353.1
ENSG00000266120	ENST00000577420.1	n.*65C>T		downstream_gene_variant		3

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

Gnomad4 FIN exome AF: 0.00

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

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.307

Alfa AF: 0.317 Hom.: 1260

Bravo AF: 0.301

Asia WGS AF: 0.287 AC: 998 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.6
DANN	Benign	0.84

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: rs7223821; hg19: chr17-28579320;