rs7183841

Variant names:

• chr15-90751667-T-C
• rs7183841
• NM_000057.4:c.800-120T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-90751667-T-C
• chr15-90751667-T-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000057.4(BLM):​c.800-120T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 797,304 control chromosomes in the GnomAD database, including 14,540 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3281 hom., cov: 32)
  • Exomes 𝑓: 0.18 (11259 hom.)
• Consequence: BLM NM_000057.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.538
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 15-90751667-T-C is Benign according to our data. Variant chr15-90751667-T-C is described in ClinVar as Benign. ClinVar VariationId is 1177546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.266 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.800-120T>C		intron	N/A	NP_000048.1	P54132
	BLM	NM_001287246.2		c.800-120T>C		intron	N/A	NP_001274175.1	P54132
	BLM	NM_001287247.2		c.800-120T>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.800-120T>C		intron	N/A	ENSP00000347232.3	P54132
	BLM	ENST00000560509.5	TSL:1	c.800-120T>C		intron	N/A	ENSP00000454158.1	H0YNU5
	BLM	ENST00000559724.5	TSL:1	n.800-120T>C		intron	N/A	ENSP00000453359.1	H0YLV8

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30548 AN: 152076 Hom.: 3280 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.180 AC: 115862 AN: 645110 Hom.: 11259 AF XY: 0.176 AC XY: 60168 AN XY: 342766

African (AFR) AF: 0.277 AC: 4738 AN: 17098

American (AMR) AF: 0.136 AC: 4317 AN: 31652

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 2966 AN: 19352

East Asian (EAS) AF: 0.234 AC: 7608 AN: 32458

South Asian (SAS) AF: 0.0952 AC: 5818 AN: 61096

European-Finnish (FIN) AF: 0.150 AC: 5838 AN: 38920

Middle Eastern (MID) AF: 0.104 AC: 351 AN: 3364

European-Non Finnish (NFE) AF: 0.192 AC: 78442 AN: 408014

Other (OTH) AF: 0.174 AC: 5784 AN: 33156

GnomAD4 genome AF: 0.201 AC: 30568 AN: 152194 Hom.: 3281 Cov.: 32 AF XY: 0.197 AC XY: 14639 AN XY: 74426

African (AFR) AF: 0.271 AC: 11232 AN: 41506

American (AMR) AF: 0.151 AC: 2301 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 533 AN: 3470

East Asian (EAS) AF: 0.243 AC: 1260 AN: 5184

South Asian (SAS) AF: 0.104 AC: 500 AN: 4826

European-Finnish (FIN) AF: 0.140 AC: 1484 AN: 10614

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12777 AN: 68008

Other (OTH) AF: 0.175 AC: 370 AN: 2114

Alfa AF: 0.0901 Hom.: 157

Bravo AF: 0.203

Asia WGS AF: 0.182 AC: 632 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Bloom syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.5
DANN	Benign	0.59
PhyloP100		0.54
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: rs7183841; hg19: chr15-91294897; COSMIC: COSV61923778; COSMIC: COSV61923778;