rs11377009

Positions:

• chr15-90803400-C-CA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000057.4(BLM):​c.3359-121_3359-120insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 794,838 control chromosomes in the GnomAD database, including 181,083 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (34669 hom., cov: 0)
  • Exomes 𝑓: 0.67 (146414 hom.)
• Consequence: BLM NM_000057.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.310

Genes affected

BLM (HGNC:1058): (BLM RecQ like helicase) The Bloom syndrome is an autosomal recessive disorder characterized by growth deficiency, microcephaly and immunodeficiency among others. It is caused by homozygous or compound heterozygous mutation in the gene encoding DNA helicase RecQ protein on chromosome 15q26. This Bloom-associated helicase unwinds a variety of DNA substrates including Holliday junction, and is involved in several pathways contributing to the maintenance of genome stability. Identification of pathogenic Bloom variants is required for heterozygote testing in at-risk families. [provided by RefSeq, May 2020]

BLM (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 15-90803400-C-CA is Benign according to our data. Variant chr15-90803400-C-CA is described in ClinVar as [Likely_benign]. Clinvar id is 210529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLM	NM_000057.4	c.3359-121_3359-120insA		intron_variant		ENST00000355112.8	NP_000048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLM	ENST00000355112.8	c.3359-121_3359-120insA		intron_variant		1	NM_000057.4	ENSP00000347232.3

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102035 AN: 151760 Hom.: 34638 Cov.: 0

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.843

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.670

GnomAD4 exome AF: 0.672 AC: 431760 AN: 642960 Hom.: 146414 AF XY: 0.670 AC XY: 224285 AN XY: 334894

Gnomad4 AFR exome AF: 0.663

Gnomad4 AMR exome AF: 0.783

Gnomad4 ASJ exome AF: 0.697

Gnomad4 EAS exome AF: 0.832

Gnomad4 SAS exome AF: 0.668

Gnomad4 FIN exome AF: 0.633

Gnomad4 NFE exome AF: 0.655

Gnomad4 OTH exome AF: 0.674

GnomAD4 genome AF: 0.672 AC: 102118 AN: 151878 Hom.: 34669 Cov.: 0 AF XY: 0.673 AC XY: 49942 AN XY: 74200

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.746

Gnomad4 ASJ AF: 0.700

Gnomad4 EAS AF: 0.843

Gnomad4 SAS AF: 0.668

Gnomad4 FIN AF: 0.632

Gnomad4 NFE AF: 0.660

Gnomad4 OTH AF: 0.671

Alfa AF: 0.677 Hom.: 4221

Bravo AF: 0.680

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 29, 2015

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs11377009; hg19: chr15-91346630;