rs9608102

Variant names:

• chr22-23302607-C-T
• rs9608102
• NM_004327.4:c.3013-6817C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004327.4(BCR):​c.3013-6817C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0989 in 152,362 control chromosomes in the GnomAD database, including 810 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 0.099 (810 hom., cov: 32)
  • Exomes 𝑓: 0.073 (0 hom.)
• Consequence: BCR NM_004327.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.06

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCR	NM_004327.4	c.3013-6817C>T		intron_variant	Intron 16 of 22	ENST00000305877.13	NP_004318.3
BCR	NM_021574.3	c.2881-6817C>T		intron_variant	Intron 15 of 21		NP_067585.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCR	ENST00000305877.13	c.3013-6817C>T		intron_variant	Intron 16 of 22	1	NM_004327.4	ENSP00000303507.8
BCR	ENST00000359540.7	c.2881-6817C>T		intron_variant	Intron 15 of 21	1		ENSP00000352535.3
BCR	ENST00000471452.1	n.382C>T		non_coding_transcript_exon_variant	Exon 2 of 2	3
BCR	ENST00000419722.6	n.238-6817C>T		intron_variant	Intron 3 of 4	5

Frequencies

GnomAD3 genomes AF: 0.0989 AC: 15039 AN: 152118 Hom.: 805 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.0803

Gnomad ASJ AF: 0.0862

Gnomad EAS AF: 0.0511

Gnomad SAS AF: 0.0679

Gnomad FIN AF: 0.0376

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0942

Gnomad OTH AF: 0.0956

GnomAD4 exome AF: 0.0726 AC: 9 AN: 124 Hom.: 0 Cov.: 0 AF XY: 0.0745 AC XY: 7 AN XY: 94

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0612

Gnomad4 OTH exome AF: 0.0833

GnomAD4 genome AF: 0.0989 AC: 15055 AN: 152238 Hom.: 810 Cov.: 32 AF XY: 0.0950 AC XY: 7070 AN XY: 74430

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.0802

Gnomad4 ASJ AF: 0.0862

Gnomad4 EAS AF: 0.0514

Gnomad4 SAS AF: 0.0671

Gnomad4 FIN AF: 0.0376

Gnomad4 NFE AF: 0.0942

Gnomad4 OTH AF: 0.0960

Alfa AF: 0.0934 Hom.: 1279

Bravo AF: 0.106

Asia WGS AF: 0.0770 AC: 267 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	0.14
DANN	Benign	0.69

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: rs9608102; hg19: chr22-23644794;