NM_004327.4:c.395G>T

Variant names:

Variant summary

Our verdict is The variant received 0 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_Moderate

The NM_004327.4(BCR):c.395G>T (p.Arg132Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant is present but has an allele frequency of zero in the gnomAD population database. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain Significance (★). Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.R132P: Likely_benign (ClinVar VariationId 725929, 1 star)

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Consequence

BCR
NM_004327.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.71

Publications

0 publications found

Variant links:

Genes affected

BCR (HGNC:1014): (BCR activator of RhoGEF and GTPase) A reciprocal translocation between chromosomes 22 and 9 produces the Philadelphia chromosome, which is often found in patients with chronic myelogenous leukemia. The chromosome 22 breakpoint for this translocation is located within the BCR gene. The translocation produces a fusion protein which is encoded by sequence from both BCR and ABL, the gene at the chromosome 9 breakpoint. Although the BCR-ABL fusion protein has been extensively studied, the function of the normal BCR gene product is not clear. The unregulated tyrosine kinase activity of BCR-ABL1 contributes to the immortality of leukaemic cells. The BCR protein has serine/threonine kinase activity and is a GTPase-activating protein for p21rac and other kinases. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2020]

BCR links:

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new If you want to explore the variant's impact on the transcript NM_004327.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 points.

PM2

Very rare in gnomAD for AD/XL gene (popmax AF < threshold/10) — PM2; GnomAD popmax AF = 0 — very rare for AD/XL gene (threshold 0.0001) — PM2 moderate.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Moderate).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_004327.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCR	NM_004327.4	MANE Select	c.395G>T	p.Arg132Leu	missense	Exon 1 of 23	NP_004318.3
	BCR	NM_021574.3		c.395G>T	p.Arg132Leu	missense	Exon 1 of 22	NP_067585.2	P11274-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCR	ENST00000305877.13	TSL:1 MANE Select	c.395G>T	p.Arg132Leu	missense	Exon 1 of 23	ENSP00000303507.8	P11274-1
BCR	ENST00000359540.7	TSL:1	c.395G>T	p.Arg132Leu	missense	Exon 1 of 22	ENSP00000352535.3	P11274-2
BCR	ENST00000928588.1		c.395G>T	p.Arg132Leu	missense	Exon 1 of 23	ENSP00000598647.1	A0ACI8THE4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00

AC:

AN:

1353998

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

665766

African (AFR)

AF:

0.00

AC:

AN:

29180

American (AMR)

AF:

0.00

AC:

AN:

29318

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20512

East Asian (EAS)

AF:

0.00

AC:

AN:

36922

South Asian (SAS)

AF:

0.00

AC:

AN:

71384

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39728

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4668

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1066534

Other (OTH)

AF:

0.00

AC:

AN:

55752

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.74

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.81

M_CAP

Benign

0.068

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PhyloP100

2.7

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.4

REVEL

Benign

0.065

Sift

Uncertain

0.011

Sift4G

Uncertain

0.0080

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.066

gMVP

0.34

Mutation Taster

=88/12

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over