15-90794393-ATT-AT

Variant names:

• chr15-90794393-AT-A
• rs3214113
• NM_000057.4:c.3210+44delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000057.4(BLM):​c.3210+44delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,435,330 control chromosomes in the GnomAD database, including 21,695 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2314 hom., cov: 28)
  • Exomes 𝑓: 0.17 (19381 hom.)
• Consequence: BLM NM_000057.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.97
• Publications: 3 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: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, Laboratory for Molecular Medicine, Orphanet, Myriad Women’s Health
• 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 -16 ACMG points.

• BP6: Variant 15-90794393-AT-A is Benign according to our data. Variant chr15-90794393-AT-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 254779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 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.3210+44delT		intron	N/A	NP_000048.1	P54132
	BLM	NM_001287246.2		c.3210+44delT		intron	N/A	NP_001274175.1	P54132
	BLM	NM_001287247.2		c.3210+44delT		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.3210+37delT		intron	N/A	ENSP00000347232.3	P54132
	BLM	ENST00000560509.5	TSL:1	c.3210+37delT		intron	N/A	ENSP00000454158.1	H0YNU5
	BLM	ENST00000559724.5	TSL:1	n.*2134+37delT		intron	N/A	ENSP00000453359.1	H0YLV8

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26093 AN: 151742 Hom.: 2314 Cov.: 28

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0956

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.0910

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.161

GnomAD2 exomes AF: 0.152 AC: 19006 AN: 124958 AF XY: 0.149

Gnomad AFR exome AF: 0.183

Gnomad AMR exome AF: 0.0984

Gnomad ASJ exome AF: 0.163

Gnomad EAS exome AF: 0.190

Gnomad FIN exome AF: 0.145

Gnomad NFE exome AF: 0.181

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.169 AC: 216779 AN: 1283470 Hom.: 19381 Cov.: 16 AF XY: 0.167 AC XY: 106351 AN XY: 636028

African (AFR) AF: 0.179 AC: 4959 AN: 27692

American (AMR) AF: 0.0987 AC: 2625 AN: 26604

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 3740 AN: 23004

East Asian (EAS) AF: 0.174 AC: 5943 AN: 34246

South Asian (SAS) AF: 0.0864 AC: 5803 AN: 67148

European-Finnish (FIN) AF: 0.145 AC: 6627 AN: 45808

Middle Eastern (MID) AF: 0.133 AC: 489 AN: 3676

European-Non Finnish (NFE) AF: 0.177 AC: 177874 AN: 1002132

Other (OTH) AF: 0.164 AC: 8719 AN: 53160

GnomAD4 genome AF: 0.172 AC: 26116 AN: 151860 Hom.: 2314 Cov.: 28 AF XY: 0.167 AC XY: 12399 AN XY: 74208

African (AFR) AF: 0.185 AC: 7686 AN: 41448

American (AMR) AF: 0.117 AC: 1782 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 595 AN: 3472

East Asian (EAS) AF: 0.179 AC: 926 AN: 5182

South Asian (SAS) AF: 0.0919 AC: 442 AN: 4810

European-Finnish (FIN) AF: 0.146 AC: 1525 AN: 10476

Middle Eastern (MID) AF: 0.151 AC: 44 AN: 292

European-Non Finnish (NFE) AF: 0.187 AC: 12690 AN: 67904

Other (OTH) AF: 0.161 AC: 339 AN: 2104

Alfa AF: 0.185 Hom.: 514

Bravo AF: 0.170

Asia WGS AF: 0.139 AC: 481 AN: 3460

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.0
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: rs3214113; hg19: chr15-91337623;