22-23181415-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004327.4(BCR):c.455C>T(p.Ala152Val) variant causes a missense change. The variant allele was found at a frequency of 0.0021 in 1,575,312 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A152T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 15 hom. )

Consequence

BCR
NM_004327.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.47

Publications

4 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009052664).

BP6

Variant 22-23181415-C-T is Benign according to our data. Variant chr22-23181415-C-T is described in ClinVar as Benign. ClinVar VariationId is 708500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 311 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.455C>T	p.Ala152Val	missense	Exon 1 of 23	NP_004318.3
	BCR	NM_021574.3		c.455C>T	p.Ala152Val	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.455C>T	p.Ala152Val	missense	Exon 1 of 23	ENSP00000303507.8	P11274-1
BCR	ENST00000359540.7	TSL:1	c.455C>T	p.Ala152Val	missense	Exon 1 of 22	ENSP00000352535.3	P11274-2
BCR	ENST00000928588.1		c.455C>T	p.Ala152Val	missense	Exon 1 of 23	ENSP00000598647.1

Frequencies

GnomAD3 genomes

AF:

0.00205

AC:

311

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0143

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00215

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00272

AC:

589

AN:

216466

AF XY:

0.00276

show subpopulations

Gnomad AFR exome

AF:

0.000219

Gnomad AMR exome

AF:

0.0000332

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0150

Gnomad NFE exome

AF:

0.00303

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00211

AC:

3005

AN:

1423140

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

1483

AN XY:

703880

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

32248

American (AMR)

AF:

0.000123

AC:

AN:

40496

Ashkenazi Jewish (ASJ)

AF:

0.0000412

AC:

AN:

24280

East Asian (EAS)

AF:

0.00

AC:

AN:

38930

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82842

European-Finnish (FIN)

AF:

0.0153

AC:

747

AN:

48806

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5586

European-Non Finnish (NFE)

AF:

0.00197

AC:

2154

AN:

1091448

Other (OTH)

AF:

0.00154

AC:

AN:

58504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

190

380

570

760

950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<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:

0.00204

AC:

311

AN:

152172

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

177

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41552

American (AMR)

AF:

0.000196

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0143

AC:

151

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00215

AC:

146

AN:

67974

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.00174

Hom.:

Bravo

AF:

0.000926

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000983

AC:

ExAC

AF:

0.00305

AC:

364

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.0091

MetaSVM

Benign

-0.91

MutationAssessor

Benign

2.0

PhyloP100

5.5

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.97

REVEL

Benign

0.15

Sift

Benign

0.072

Sift4G

Uncertain

0.0090

Polyphen

1.0

Vest4

0.60

MVP

0.56

MPC

0.73

ClinPred

0.043

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.16

gMVP

0.46

Mutation Taster

=86/14

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