rs7175811

Variant names:

• chr15-90788316-G-A
• rs7175811
• NM_000057.4:c.2824-2333G>A

Variant summary

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

The NM_000057.4(BLM):​c.2824-2333G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 151,852 control chromosomes in the GnomAD database, including 17,207 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 0.44 (17207 hom., cov: 31)
• Consequence: BLM NM_000057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.725
• Publications: 17 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Myriad Women’s Health, Genomics England PanelApp, ClinGen, Laboratory for Molecular Medicine
• osteosarcoma

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

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.713 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLM	NM_000057.4	MANE Select	c.2824-2333G>A		intron	N/A	NP_000048.1	P54132
	BLM	NM_001287246.2		c.2824-2333G>A		intron	N/A	NP_001274175.1	P54132
	BLM	NM_001287247.2		c.2824-2333G>A		intron	N/A	NP_001274176.1	H0YNU5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLM	ENST00000355112.8	TSL:1 MANE Select	c.2824-2333G>A		intron	N/A	ENSP00000347232.3	P54132
	BLM	ENST00000560509.5	TSL:1	c.2824-2333G>A		intron	N/A	ENSP00000454158.1	H0YNU5
	BLM	ENST00000559724.5	TSL:1	n.*1748-2333G>A		intron	N/A	ENSP00000453359.1	H0YLV8

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67173 AN: 151734 Hom.: 17166 Cov.: 31

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.398

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.443 AC: 67274 AN: 151852 Hom.: 17207 Cov.: 31 AF XY: 0.436 AC XY: 32368 AN XY: 74194

African (AFR) AF: 0.720 AC: 29835 AN: 41418

American (AMR) AF: 0.327 AC: 4986 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 955 AN: 3470

East Asian (EAS) AF: 0.294 AC: 1517 AN: 5164

South Asian (SAS) AF: 0.254 AC: 1222 AN: 4808

European-Finnish (FIN) AF: 0.384 AC: 4037 AN: 10508

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23507 AN: 67910

Other (OTH) AF: 0.397 AC: 836 AN: 2106

Alfa AF: 0.366 Hom.: 46491

Bravo AF: 0.452

Asia WGS AF: 0.298 AC: 1037 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.63
PhyloP100		-0.72
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: rs7175811; hg19: chr15-91331546;