20-53957507-C-T

Variant names:

• chr20-53957507-C-T
• rs147195366
• NM_001366298.2:c.1486-10G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_001366298.2(BCAS1):​c.1486-10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,613,022 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0065 (10 hom., cov: 32)
  • Exomes 𝑓: 0.00066 (16 hom.)
• Consequence: BCAS1 NM_001366298.2 intron
• Scores: Splicing: ADA: 0.0004062
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.20
• Publications: 0 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 20-53957507-C-T is Benign according to our data. Variant chr20-53957507-C-T is described in ClinVar as Benign. ClinVar VariationId is 710981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00652 (993/152308) while in subpopulation AFR AF = 0.0224 (933/41562). AF 95% confidence interval is 0.0213. There are 10 homozygotes in GnomAd4. There are 460 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366298.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAS1	NM_001366298.2	MANE Select	c.1486-10G>A		intron	N/A	NP_001353227.1	A0A8I5KUN3
	BCAS1	NM_003657.4		c.1351-10G>A		intron	N/A	NP_003648.2	O75363-1
	BCAS1	NM_001366295.2		c.1309-10G>A		intron	N/A	NP_001353224.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAS1	ENST00000688948.1	MANE Select	c.1486-10G>A		intron	N/A	ENSP00000508731.1	A0A8I5KUN3
	BCAS1	ENST00000395961.7	TSL:1	c.1351-10G>A		intron	N/A	ENSP00000379290.3	O75363-1
	BCAS1	ENST00000371435.6	TSL:1	c.1183-3812G>A		intron	N/A	ENSP00000360490.2	G3XAF7

Frequencies

GnomAD3 genomes AF: 0.00651 AC: 991 AN: 152190 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0224

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00175 AC: 439 AN: 251382 AF XY: 0.00130

Gnomad AFR exome AF: 0.0243

Gnomad AMR exome AF: 0.000983

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000792

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000661 AC: 966 AN: 1460714 Hom.: 16 Cov.: 31 AF XY: 0.000590 AC XY: 429 AN XY: 726744

African (AFR) AF: 0.0234 AC: 782 AN: 33440

American (AMR) AF: 0.00121 AC: 54 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5762

European-Non Finnish (NFE) AF: 0.0000288 AC: 32 AN: 1111016

Other (OTH) AF: 0.00139 AC: 84 AN: 60336

GnomAD4 genome AF: 0.00652 AC: 993 AN: 152308 Hom.: 10 Cov.: 32 AF XY: 0.00618 AC XY: 460 AN XY: 74484

African (AFR) AF: 0.0224 AC: 933 AN: 41562

American (AMR) AF: 0.00255 AC: 39 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68026

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.00505 Hom.: 3

Bravo AF: 0.00723

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	16
DANN	Benign	0.73
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00041
dbscSNV1_RF	Benign	0.018
SpliceAI score (max)		0.090		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: rs147195366; hg19: chr20-52574046;