dbSNP rs2227939: BCR:p.Asn900Asn (chr22-23289614-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_004327.4(BCR):c.2700T>C(p.Asn900Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,612,806 control chromosomes in the GnomAD database, including 72,629 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.34 ( 10118 hom., cov: 34)

Exomes 𝑓: 0.28 ( 62511 hom. )

Consequence

BCR
NM_004327.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.579

Publications

18 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:

ENSG00000296232 (HGNC:):

ENSG00000296232 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP7

Synonymous conserved (PhyloP=0.579 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCR	NM_004327.4 link	c.2700T>C	p.Asn900Asn	synonymous_variant	Exon 13 of 23	ENST00000305877.13	NP_004318.3	P11274-1
BCR	NM_021574.3 link	c.2700T>C	p.Asn900Asn	synonymous_variant	Exon 13 of 22		NP_067585.2	P11274-2
LOC107985554	XR_001755448.2 link	n.315+600A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCR	ENST00000305877.13 link	c.2700T>C	p.Asn900Asn	synonymous_variant	Exon 13 of 23	1	NM_004327.4	ENSP00000303507.8		P11274-1

Frequencies

GnomAD3 genomes

AF:

0.344

AC:

52240

AN:

152022

Hom.:

10101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.517

Gnomad AMI

AF:

0.259

Gnomad AMR

AF:

0.326

Gnomad ASJ

AF:

0.374

Gnomad EAS

AF:

0.0605

Gnomad SAS

AF:

0.286

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.344

GnomAD2 exomes

AF:

0.286

AC:

71806

AN:

250794

AF XY:

0.286

show subpopulations

Gnomad AFR exome

AF:

0.521

Gnomad AMR exome

AF:

0.291

Gnomad ASJ exome

AF:

0.378

Gnomad EAS exome

AF:

0.0577

Gnomad FIN exome

AF:

0.188

Gnomad NFE exome

AF:

0.293

Gnomad OTH exome

AF:

0.301

GnomAD4 exome

AF:

0.284

AC:

415462

AN:

1460666

Hom.:

62511

Cov.:

AF XY:

0.286

AC XY:

207730

AN XY:

726666

show subpopulations

African (AFR)

AF:

0.538

AC:

17980

AN:

33446

American (AMR)

AF:

0.303

AC:

13524

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.378

AC:

9871

AN:

26126

East Asian (EAS)

AF:

0.0610

AC:

2423

AN:

39690

South Asian (SAS)

AF:

0.306

AC:

26409

AN:

86194

European-Finnish (FIN)

AF:

0.196

AC:

10457

AN:

53412

Middle Eastern (MID)

AF:

0.440

AC:

2536

AN:

5768

European-Non Finnish (NFE)

AF:

0.283

AC:

314321

AN:

1111020

Other (OTH)

AF:

0.297

AC:

17941

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

14880

29760

44640

59520

74400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10370

20740

31110

41480

51850

<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:

0.344

AC:

52304

AN:

152140

Hom.:

10118

Cov.:

AF XY:

0.336

AC XY:

24999

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.517

AC:

21447

AN:

41460

American (AMR)

AF:

0.326

AC:

4989

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.374

AC:

1300

AN:

3472

East Asian (EAS)

AF:

0.0604

AC:

313

AN:

5182

South Asian (SAS)

AF:

0.286

AC:

1379

AN:

4824

European-Finnish (FIN)

AF:

0.189

AC:

2007

AN:

10608

Middle Eastern (MID)

AF:

0.418

AC:

123

AN:

294

European-Non Finnish (NFE)

AF:

0.291

AC:

19789

AN:

67978

Other (OTH)

AF:

0.341

AC:

721

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1707

3413

5120

6826

8533

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

498

996

1494

1992

2490

<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:

0.323

Hom.:

7084

Bravo

AF:

0.362

Asia WGS

AF:

0.189

AC:

661

AN:

3478

EpiCase

AF:

0.315

EpiControl

AF:

0.318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

6.8

(source)

DANN

Benign

0.60

PhyloP100

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over