chr15-90717714-G-C

Variant names:

• chr15-90717714-G-C
• rs7163120
• NM_000057.4:c.-5+274G>C

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.-5+274G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 152,302 control chromosomes in the GnomAD database, including 1,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.092 (1960 hom., cov: 32)
• Consequence: BLM NM_000057.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.29
• Publications: 2 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=-0.92).
• BP6: Variant 15-90717714-G-C is Benign according to our data. Variant chr15-90717714-G-C is described in ClinVar as Benign. ClinVar VariationId is 1291120.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 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.-5+274G>C		intron	N/A	NP_000048.1	P54132
	BLM	NM_001287246.2		c.-115+274G>C		intron	N/A	NP_001274175.1	P54132
	BLM	NM_001287247.2		c.-5+274G>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.-5+274G>C		intron	N/A	ENSP00000347232.3	P54132
	BLM	ENST00000560509.5	TSL:1	c.-5+274G>C		intron	N/A	ENSP00000454158.1	H0YNU5
	BLM	ENST00000559724.5	TSL:1	n.-5+274G>C		intron	N/A	ENSP00000453359.1	H0YLV8

Frequencies

GnomAD3 genomes AF: 0.0916 AC: 13938 AN: 152184 Hom.: 1948 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0383

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.0473

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.0385

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00342

Gnomad OTH AF: 0.0716

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

GnomAD4 genome AF: 0.0918 AC: 13985 AN: 152302 Hom.: 1960 Cov.: 32 AF XY: 0.0911 AC XY: 6782 AN XY: 74482

African (AFR) AF: 0.295 AC: 12254 AN: 41536

American (AMR) AF: 0.0383 AC: 586 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 36 AN: 3470

East Asian (EAS) AF: 0.0468 AC: 243 AN: 5192

South Asian (SAS) AF: 0.0122 AC: 59 AN: 4834

European-Finnish (FIN) AF: 0.0385 AC: 409 AN: 10612

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.00343 AC: 233 AN: 68028

Other (OTH) AF: 0.0709 AC: 150 AN: 2116

Alfa AF: 0.0554 Hom.: 130

Bravo AF: 0.103

Asia WGS AF: 0.0510 AC: 175 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	-0.92
CADD	Benign	0.93
DANN	Benign	0.60
PhyloP100		-1.3
PromoterAI		0.023	Neutral
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: rs7163120; hg19: chr15-91260945;