chr22-23199301-C-T

Position:

• chr22-23199301-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97

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 (HGNC:):

ACMG classification

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	Protein	UniProt
BCR	NM_004327.4	c.1279+17062C>T		intron_variant		ENST00000305877.13	NP_004318.3
BCR	NM_021574.3	c.1279+17062C>T		intron_variant			NP_067585.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCR	ENST00000305877.13	c.1279+17062C>T		intron_variant		1	NM_004327.4	ENSP00000303507.8

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34588 AN: 151902 Hom.: 4450 Cov.: 31

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

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.: 0 AF XY: 0.253 AC XY: 53112 AN XY: 209892

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.: 31 AF XY: 0.230 AC XY: 17102 AN XY: 74292

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

Other links and lift over

dbSNP: rs2071436; hg19: chr22-23541488; COSMIC: COSV59927241;