NM_001366298.2:c.764G>A

Variant names:

• chr20-53996010-C-T
• rs6022903
• NM_001366298.2:c.764G>A

Variant summary

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

The NM_001366298.2(BCAS1):​c.764G>A​(p.Gly255Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0568 in 1,609,932 control chromosomes in the GnomAD database, including 6,358 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (2591 hom., cov: 32)
  • Exomes 𝑓: 0.050 (3767 hom.)
• Consequence: BCAS1 NM_001366298.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.780
• Publications: 16 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 (MetaRNN=0.0042648017).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

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.764G>A	p.Gly255Glu	missense	Exon 5 of 13	NP_001353227.1	A0A8I5KUN3
	BCAS1	NM_003657.4		c.764G>A	p.Gly255Glu	missense	Exon 5 of 12	NP_003648.2	O75363-1
	BCAS1	NM_001366295.2		c.764G>A	p.Gly255Glu	missense	Exon 5 of 11	NP_001353224.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAS1	ENST00000688948.1	MANE Select	c.764G>A	p.Gly255Glu	missense	Exon 5 of 13	ENSP00000508731.1	A0A8I5KUN3
	BCAS1	ENST00000395961.7	TSL:1	c.764G>A	p.Gly255Glu	missense	Exon 5 of 12	ENSP00000379290.3	O75363-1
	BCAS1	ENST00000371435.6	TSL:1	c.764G>A	p.Gly255Glu	missense	Exon 5 of 10	ENSP00000360490.2	G3XAF7

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19055 AN: 152054 Hom.: 2584 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0576

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.0144

Gnomad SAS AF: 0.0767

Gnomad FIN AF: 0.0411

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0416

Gnomad OTH AF: 0.0909

GnomAD2 exomes AF: 0.0629 AC: 15599 AN: 248188 AF XY: 0.0598

Gnomad AFR exome AF: 0.352

Gnomad AMR exome AF: 0.0358

Gnomad ASJ exome AF: 0.0131

Gnomad EAS exome AF: 0.0150

Gnomad FIN exome AF: 0.0452

Gnomad NFE exome AF: 0.0422

Gnomad OTH exome AF: 0.0494

GnomAD4 exome AF: 0.0497 AC: 72425 AN: 1457758 Hom.: 3767 Cov.: 30 AF XY: 0.0499 AC XY: 36172 AN XY: 725116

African (AFR) AF: 0.362 AC: 12020 AN: 33246

American (AMR) AF: 0.0384 AC: 1692 AN: 44024

Ashkenazi Jewish (ASJ) AF: 0.0125 AC: 324 AN: 25996

East Asian (EAS) AF: 0.00964 AC: 382 AN: 39644

South Asian (SAS) AF: 0.0759 AC: 6494 AN: 85610

European-Finnish (FIN) AF: 0.0450 AC: 2401 AN: 53334

Middle Eastern (MID) AF: 0.0629 AC: 362 AN: 5752

European-Non Finnish (NFE) AF: 0.0405 AC: 44955 AN: 1109998

Other (OTH) AF: 0.0631 AC: 3795 AN: 60154

GnomAD4 genome AF: 0.125 AC: 19094 AN: 152174 Hom.: 2591 Cov.: 32 AF XY: 0.121 AC XY: 9018 AN XY: 74390

African (AFR) AF: 0.343 AC: 14238 AN: 41458

American (AMR) AF: 0.0574 AC: 878 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3472

East Asian (EAS) AF: 0.0144 AC: 75 AN: 5194

South Asian (SAS) AF: 0.0767 AC: 370 AN: 4822

European-Finnish (FIN) AF: 0.0411 AC: 436 AN: 10598

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

European-Non Finnish (NFE) AF: 0.0416 AC: 2831 AN: 68018

Other (OTH) AF: 0.0900 AC: 190 AN: 2112

Alfa AF: 0.0658 Hom.: 4281

Bravo AF: 0.136

TwinsUK AF: 0.0410 AC: 152

ALSPAC AF: 0.0348 AC: 134

ESP6500AA AF: 0.338 AC: 1491

ESP6500EA AF: 0.0409 AC: 352

ExAC AF: 0.0707 AC: 8585

Asia WGS AF: 0.0610 AC: 213 AN: 3478

EpiCase AF: 0.0451

EpiControl AF: 0.0426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.52
DEOGEN2	Benign	0.014	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.60	T
MetaRNN	Benign	0.0043	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.67	N
PhyloP100		0.78
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.049
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0020	B
Vest4		0.014
MPC		0.11
ClinPred		0.00048	T
GERP RS		0.43
PromoterAI		0.011	Neutral
Varity_R		0.032
gMVP		0.026
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: rs6022903; hg19: chr20-52612549; COSMIC: COSV105299114; COSMIC: COSV105299114;