Genetic Variant BCR:p.Ala131Ala (chr22-23181353-C-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_004327.4(BCR):c.393C>A(p.Ala131Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000863 in 1,506,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000087 ( 0 hom. )

Consequence

BCR
NM_004327.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.269

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 22-23181353-C-A is Benign according to our data. Variant chr22-23181353-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2652957.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.269 with no splicing effect.

BS2

High AC in GnomAd4 at 12 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004327.4. 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
	BCR	NM_004327.4	MANE Select	c.393C>A	p.Ala131Ala	synonymous	Exon 1 of 23	NP_004318.3
	BCR	NM_021574.3		c.393C>A	p.Ala131Ala	synonymous	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.393C>A	p.Ala131Ala	synonymous	Exon 1 of 23	ENSP00000303507.8	P11274-1
BCR	ENST00000359540.7	TSL:1	c.393C>A	p.Ala131Ala	synonymous	Exon 1 of 22	ENSP00000352535.3	P11274-2
BCR	ENST00000928588.1		c.393C>A	p.Ala131Ala	synonymous	Exon 1 of 23	ENSP00000598647.1

Frequencies

GnomAD3 genomes

AF:

0.0000790

AC:

AN:

151846

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000521

AC:

AN:

134368

AF XY:

0.0000801

show subpopulations

Gnomad AFR exome

AF:

0.000113

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000938

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000871

AC:

118

AN:

1354490

Hom.:

Cov.:

AF XY:

0.0000826

AC XY:

AN XY:

665986

show subpopulations

African (AFR)

AF:

0.0000683

AC:

AN:

29266

American (AMR)

AF:

0.00

AC:

AN:

29282

Ashkenazi Jewish (ASJ)

AF:

0.0000486

AC:

AN:

20566

East Asian (EAS)

AF:

0.00

AC:

AN:

36954

South Asian (SAS)

AF:

0.00

AC:

AN:

71656

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39662

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4624

European-Non Finnish (NFE)

AF:

0.000107

AC:

114

AN:

1066714

Other (OTH)

AF:

0.0000179

AC:

AN:

55766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000790

AC:

AN:

151958

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41516

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5132

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10508

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

67916

Other (OTH)

AF:

0.00

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000642

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

2.2

(source)

DANN

Benign

0.70

PhyloP100

-0.27

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=100/0

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over