rs2270132

Variant names:

• chr15-90808638-A-C
• rs2270132
• NM_000057.4:c.3752-499A>C

Your query was ambiguous. Multiple possible variants found:

• chr15-90808638-A-C
• chr15-90808638-A-G
• chr15-90808638-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000057.4(BLM):​c.3752-499A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 199,500 control chromosomes in the GnomAD database, including 15,646 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 0.36 (11246 hom., cov: 33)
  • Exomes 𝑓: 0.41 (4400 hom.)
• Consequence: BLM NM_000057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 21 publications found

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 Gene-Disease associations (from GenCC):

• Bloom syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Myriad Women’s Health, Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine, Orphanet, Genomics England PanelApp, ClinGen
• osteosarcoma

  Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
• breast cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
• hereditary nonpolyposis colon cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

ENSG00000300894 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000057.4. 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
	BLM	NM_000057.4	MANE Select	c.3752-499A>C		intron	N/A	NP_000048.1
	BLM	NM_001287246.2		c.3752-499A>C		intron	N/A	NP_001274175.1
	BLM	NM_001287247.2		c.3359-499A>C		intron	N/A	NP_001274176.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLM	ENST00000355112.8	TSL:1 MANE Select	c.3752-499A>C		intron	N/A	ENSP00000347232.3
	BLM	ENST00000560509.5	TSL:1	c.3359-499A>C		intron	N/A	ENSP00000454158.1
	BLM	ENST00000559724.5	TSL:1	n.*2676-499A>C		intron	N/A	ENSP00000453359.1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54742 AN: 152088 Hom.: 11250 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.392

GnomAD4 exome AF: 0.411 AC: 19432 AN: 47294 Hom.: 4400 AF XY: 0.412 AC XY: 10098 AN XY: 24492

African (AFR) AF: 0.143 AC: 223 AN: 1558

American (AMR) AF: 0.550 AC: 1895 AN: 3446

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 419 AN: 990

East Asian (EAS) AF: 0.549 AC: 1548 AN: 2818

South Asian (SAS) AF: 0.480 AC: 2799 AN: 5834

European-Finnish (FIN) AF: 0.353 AC: 521 AN: 1474

Middle Eastern (MID) AF: 0.371 AC: 69 AN: 186

European-Non Finnish (NFE) AF: 0.385 AC: 10969 AN: 28518

Other (OTH) AF: 0.400 AC: 989 AN: 2470

GnomAD4 genome AF: 0.360 AC: 54765 AN: 152206 Hom.: 11246 Cov.: 33 AF XY: 0.365 AC XY: 27147 AN XY: 74412

African (AFR) AF: 0.158 AC: 6571 AN: 41544

American (AMR) AF: 0.520 AC: 7947 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1536 AN: 3468

East Asian (EAS) AF: 0.554 AC: 2874 AN: 5190

South Asian (SAS) AF: 0.481 AC: 2319 AN: 4826

European-Finnish (FIN) AF: 0.372 AC: 3932 AN: 10574

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28088 AN: 67988

Other (OTH) AF: 0.393 AC: 831 AN: 2114

Alfa AF: 0.390 Hom.: 8713

Bravo AF: 0.362

Asia WGS AF: 0.472 AC: 1642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.013
DANN	Benign	0.70
PhyloP100		-1.1
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: rs2270132; hg19: chr15-91351868;