rs2238335

Variant names:

• chr15-90747136-G-C
• rs2238335
• NM_000057.4:c.-4-253G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-90747136-G-C
• chr15-90747136-G-A
• chr15-90747136-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000057.4(BLM):​c.-4-253G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0721 in 151,248 control chromosomes in the GnomAD database, including 718 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.072 (718 hom., cov: 30)
• Consequence: BLM NM_000057.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.103
• Publications: 4 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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 15-90747136-G-C is Benign according to our data. Variant chr15-90747136-G-C is described in ClinVar as Benign. ClinVar VariationId is 1258326.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 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.-4-253G>C		intron	N/A	NP_000048.1	P54132
	BLM	NM_001287246.2		c.-4-253G>C		intron	N/A	NP_001274175.1	P54132
	BLM	NM_001287247.2		c.-4-253G>C		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.-4-253G>C		intron	N/A	ENSP00000347232.3	P54132
	BLM	ENST00000560509.5	TSL:1	c.-4-253G>C		intron	N/A	ENSP00000454158.1	H0YNU5
	BLM	ENST00000559724.5	TSL:1	n.-4-253G>C		intron	N/A	ENSP00000453359.1	H0YLV8

Frequencies

GnomAD3 genomes AF: 0.0720 AC: 10889 AN: 151134 Hom.: 719 Cov.: 30

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.0451

Gnomad AMR AF: 0.0489

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.0839

Gnomad SAS AF: 0.0489

Gnomad FIN AF: 0.0456

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0228

Gnomad OTH AF: 0.0599

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

GnomAD4 genome AF: 0.0721 AC: 10903 AN: 151248 Hom.: 718 Cov.: 30 AF XY: 0.0725 AC XY: 5349 AN XY: 73820

African (AFR) AF: 0.176 AC: 7231 AN: 41142

American (AMR) AF: 0.0491 AC: 746 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3466

East Asian (EAS) AF: 0.0837 AC: 431 AN: 5150

South Asian (SAS) AF: 0.0481 AC: 230 AN: 4780

European-Finnish (FIN) AF: 0.0456 AC: 472 AN: 10350

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0228 AC: 1547 AN: 67888

Other (OTH) AF: 0.0599 AC: 125 AN: 2088

Alfa AF: 0.0169 Hom.: 11

Bravo AF: 0.0773

Asia WGS AF: 0.0740 AC: 257 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.9
DANN	Benign	0.75
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2238335; hg19: chr15-91290366;