Variant 22-23315820-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004327.4(BCR):c.*298G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 478,156 control chromosomes in the GnomAD database, including 38,004 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 0.40 ( 12105 hom., cov: 31)

Exomes 𝑓: 0.39 ( 25899 hom. )

Consequence

BCR
NM_004327.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.904

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:

BCR (HGNC:):

BCR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
BCR	NM_004327.4 linkuse as main transcript	c.*298G>A	3_prime_UTR_variant	23/23	ENST00000305877.13	NP_004318.3	P11274-1
BCR	NM_021574.3 linkuse as main transcript	c.*298G>A	3_prime_UTR_variant	22/22		NP_067585.2	P11274-2
POM121L11P	use as main transcript	n.23315820G>A	intragenic_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BCR	ENST00000305877.13 linkuse as main transcript	c.*298G>A	3_prime_UTR_variant	23/23	1	NM_004327.4	ENSP00000303507.8	P11274-1
BCR	ENST00000359540.7 linkuse as main transcript	c.*298G>A	3_prime_UTR_variant	22/22	1		ENSP00000352535.3	P11274-2
BCR	ENST00000436990.2 linkuse as main transcript	n.1974G>A	non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes

AF:

0.397

AC:

60178

AN:

151586

Hom.:

12092

Cov.:

show subpopulations

Gnomad AFR

AF:

0.412

Gnomad AMI

AF:

0.380

Gnomad AMR

AF:

0.388

Gnomad ASJ

AF:

0.366

Gnomad EAS

AF:

0.594

Gnomad SAS

AF:

0.381

Gnomad FIN

AF:

0.382

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.381

Gnomad OTH

AF:

0.378

GnomAD4 exome

AF:

0.391

AC:

127607

AN:

326452

Hom.:

25899

Cov.:

AF XY:

0.388

AC XY:

66747

AN XY:

172242

show subpopulations

Gnomad4 AFR exome

AF:

0.415

Gnomad4 AMR exome

AF:

0.385

Gnomad4 ASJ exome

AF:

0.353

Gnomad4 EAS exome

AF:

0.602

Gnomad4 SAS exome

AF:

0.351

Gnomad4 FIN exome

AF:

0.397

Gnomad4 NFE exome

AF:

0.378

Gnomad4 OTH exome

AF:

0.395

GnomAD4 genome

AF:

0.397

AC:

60221

AN:

151704

Hom.:

12105

Cov.:

AF XY:

0.394

AC XY:

29248

AN XY:

74162

show subpopulations

Gnomad4 AFR

AF:

0.412

Gnomad4 AMR

AF:

0.387

Gnomad4 ASJ

AF:

0.366

Gnomad4 EAS

AF:

0.594

Gnomad4 SAS

AF:

0.378

Gnomad4 FIN

AF:

0.382

Gnomad4 NFE

AF:

0.381

Gnomad4 OTH

AF:

0.383

Alfa

AF:

0.393

Hom.:

1443

Bravo

AF:

0.402

Asia WGS

AF:

0.523

AC:

1818

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.74

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