Variant 22-23199301-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_004327.4(BCR):c.1279+17062C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 517,964 control chromosomes in the GnomAD database, including 17,697 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

Frequency

Genomes: 𝑓 0.23 ( 4450 hom., cov: 31)

Exomes 𝑓: 0.26 ( 13247 hom. )

Consequence

BCR
NM_004327.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.97

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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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 22-23199301-C-T is Benign according to our data. Variant chr22-23199301-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCR	NM_004327.4 linkuse as main transcript	c.1279+17062C>T		intron_variant		ENST00000305877.13
BCR	NM_021574.3 linkuse as main transcript	c.1279+17062C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCR	ENST00000305877.13 linkuse as main transcript	c.1279+17062C>T		intron_variant		1	NM_004327.4	P1	P11274-1

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34588

AN:

151902

Hom.:

4450

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.308

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.351

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.261

Gnomad OTH

AF:

0.225

GnomAD3 exomes

AF:

0.266

AC:

60795

AN:

228678

Hom.:

8658

AF XY:

0.261

AC XY:

32959

AN XY:

126416

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.358

Gnomad ASJ exome

AF:

0.243

Gnomad EAS exome

AF:

0.358

Gnomad SAS exome

AF:

0.193

Gnomad FIN exome

AF:

0.289

Gnomad NFE exome

AF:

0.262

Gnomad OTH exome

AF:

0.252

GnomAD4 exome

AF:

0.261

AC:

95382

AN:

365942

Hom.:

13247

Cov.:

AF XY:

0.253

AC XY:

53112

AN XY:

209892

show subpopulations

Gnomad4 AFR exome

AF:

0.115

Gnomad4 AMR exome

AF:

0.356

Gnomad4 ASJ exome

AF:

0.241

Gnomad4 EAS exome

AF:

0.366

Gnomad4 SAS exome

AF:

0.194

Gnomad4 FIN exome

AF:

0.293

Gnomad4 NFE exome

AF:

0.266

Gnomad4 OTH exome

AF:

0.251

GnomAD4 genome

AF:

0.228

AC:

34596

AN:

152022

Hom.:

4450

Cov.:

AF XY:

0.230

AC XY:

17102

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.114

Gnomad4 AMR

AF:

0.308

Gnomad4 ASJ

AF:

0.240

Gnomad4 EAS

AF:

0.351

Gnomad4 SAS

AF:

0.202

Gnomad4 FIN

AF:

0.296

Gnomad4 NFE

AF:

0.261

Gnomad4 OTH

AF:

0.222

Alfa

AF:

0.254

Hom.:

3550

Bravo

AF:

0.226

Asia WGS

AF:

0.275

AC:

955

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.17

DANN

Benign

0.76

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over