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15-90747136-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.103
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BLMNM_000057.4 linkuse as main transcriptc.-4-253G>C intron_variant ENST00000355112.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BLMENST00000355112.8 linkuse as main transcriptc.-4-253G>C intron_variant 1 NM_000057.4 P2

Frequencies

GnomAD3 genomes
AF:
0.0720
AC:
10889
AN:
151134
Hom.:
719
Cov.:
30
show subpopulations
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
show subpopulations
Gnomad4 AFR
AF:
0.176
Gnomad4 AMR
AF:
0.0491
Gnomad4 ASJ
AF:
0.0202
Gnomad4 EAS
AF:
0.0837
Gnomad4 SAS
AF:
0.0481
Gnomad4 FIN
AF:
0.0456
Gnomad4 NFE
AF:
0.0228
Gnomad4 OTH
AF:
0.0599
Alfa
AF:
0.0169
Hom.:
11
Bravo
AF:
0.0773
Asia WGS
AF:
0.0740
AC:
257
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 23, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
Cadd
Benign
7.9
Dann
Benign
0.75

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2238335; hg19: chr15-91290366; API