20-53993957-C-G

Variant names:

• chr20-53993957-C-G
• rs2276498
• NM_001366298.2:c.927+1055G>C

Variant summary

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

The NM_001366298.2(BCAS1):​c.927+1055G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,202 control chromosomes in the GnomAD database, including 1,793 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 0.14 (1793 hom., cov: 32)
• Consequence: BCAS1 NM_001366298.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.962
• Publications: 6 publications found

Genes affected

BCAS1 (HGNC:974): (brain enriched myelin associated protein 1) This gene resides in a region at 20q13 which is amplified in a variety of tumor types and associated with more aggressive tumor phenotypes. Among the genes identified from this region, it was found to be highly expressed in three amplified breast cancer cell lines and in one breast tumor without amplification at 20q13.2. However, this gene is not in the common region of maximal amplification and its expression was not detected in the breast cancer cell line MCF7, in which this region is highly amplified. Although not consistently expressed, this gene is a candidate oncogene. [provided by RefSeq, Apr 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAS1	NM_001366298.2	c.927+1055G>C		intron_variant	Intron 6 of 12	ENST00000688948.1	NP_001353227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAS1	ENST00000688948.1	c.927+1055G>C		intron_variant	Intron 6 of 12		NM_001366298.2	ENSP00000508731.1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20768 AN: 152082 Hom.: 1793 Cov.: 32

Gnomad AFR AF: 0.0379

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.137

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.136 AC: 20771 AN: 152202 Hom.: 1793 Cov.: 32 AF XY: 0.139 AC XY: 10373 AN XY: 74408

African (AFR) AF: 0.0378 AC: 1569 AN: 41536

American (AMR) AF: 0.139 AC: 2125 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 436 AN: 3468

East Asian (EAS) AF: 0.262 AC: 1357 AN: 5178

South Asian (SAS) AF: 0.140 AC: 674 AN: 4826

European-Finnish (FIN) AF: 0.224 AC: 2364 AN: 10574

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11861 AN: 67998

Other (OTH) AF: 0.137 AC: 290 AN: 2116

Alfa AF: 0.157 Hom.: 235

Bravo AF: 0.125

Asia WGS AF: 0.189 AC: 654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.084
DANN	Benign	0.37
PhyloP100		-0.96
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: rs2276498; hg19: chr20-52610496;