rs180817

Variant names:

• chr22-23315820-G-A
• rs180817
• NM_004327.4:c.*298G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.904
• Publications: 14 publications found

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]

POM121L11P (HGNC:35447):

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCR	NM_004327.4	MANE Select	c.*298G>A		3_prime_UTR	Exon 23 of 23	NP_004318.3
	BCR	NM_021574.3		c.*298G>A		3_prime_UTR	Exon 22 of 22	NP_067585.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCR	ENST00000305877.13	TSL:1 MANE Select	c.*298G>A		3_prime_UTR	Exon 23 of 23	ENSP00000303507.8
	BCR	ENST00000359540.7	TSL:1	c.*298G>A		3_prime_UTR	Exon 22 of 22	ENSP00000352535.3
	BCR	ENST00000928588.1		c.*298G>A		3_prime_UTR	Exon 23 of 23	ENSP00000598647.1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60178 AN: 151586 Hom.: 12092 Cov.: 31

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.: 0 AF XY: 0.388 AC XY: 66747 AN XY: 172242

African (AFR) AF: 0.415 AC: 4203 AN: 10128

American (AMR) AF: 0.385 AC: 5949 AN: 15458

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 3885 AN: 11002

East Asian (EAS) AF: 0.602 AC: 12787 AN: 21228

South Asian (SAS) AF: 0.351 AC: 16102 AN: 45840

European-Finnish (FIN) AF: 0.397 AC: 5597 AN: 14084

Middle Eastern (MID) AF: 0.313 AC: 431 AN: 1376

European-Non Finnish (NFE) AF: 0.378 AC: 71266 AN: 188628

Other (OTH) AF: 0.395 AC: 7387 AN: 18708

GnomAD4 genome AF: 0.397 AC: 60221 AN: 151704 Hom.: 12105 Cov.: 31 AF XY: 0.394 AC XY: 29248 AN XY: 74162

African (AFR) AF: 0.412 AC: 17007 AN: 41240

American (AMR) AF: 0.387 AC: 5914 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1268 AN: 3468

East Asian (EAS) AF: 0.594 AC: 3048 AN: 5132

South Asian (SAS) AF: 0.378 AC: 1824 AN: 4820

European-Finnish (FIN) AF: 0.382 AC: 4034 AN: 10558

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25866 AN: 67906

Other (OTH) AF: 0.383 AC: 809 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	14
DANN	Benign	0.74
PhyloP100		0.90
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs180817; hg19: chr22-23658007; COSMIC: COSV59934993; COSMIC: COSV59934993;