20-50876068-C-T

Variant names:

• chr20-50876068-C-T
• rs762515527
• ENST00000358791.9:c.561C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_017843.4(BCAS4):​c.561C>T​(p.Ser187Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00068 in 454,578 control chromosomes in the GnomAD database, including 3 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. Synonymous variant affecting the same amino acid position (i.e. S187S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00079 (3 hom.)
• Consequence: BCAS4 NM_017843.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 1 publications found

Genes affected

BCAS4 (HGNC:14367): (breast carcinoma amplified sequence 4) Predicted to be part of BLOC-1 complex. [provided by Alliance of Genome Resources, Apr 2022]

LOC124904929 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP7: Synonymous conserved (PhyloP=-1.06 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017843.4. 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
	BCAS4	NM_198799.4	MANE Select	c.400-418C>T		intron	N/A	NP_942094.3	A0A804CEY2
	BCAS4	NM_017843.4		c.561C>T	p.Ser187Ser	synonymous	Exon 5 of 6	NP_060313.3	Q8TDM0-1
	BCAS4	NM_001010974.2		c.355-418C>T		intron	N/A	NP_001010974.1	Q8TDM0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAS4	ENST00000358791.9	TSL:1	c.561C>T	p.Ser187Ser	synonymous	Exon 5 of 6	ENSP00000351642.5	Q8TDM0-1
	BCAS4	ENST00000609336.5	TSL:1	c.471C>T	p.Ser157Ser	synonymous	Exon 5 of 6	ENSP00000477167.1	A0A0C4DGS6
	BCAS4	ENST00000371608.8	TSL:1 MANE Select	c.400-418C>T		intron	N/A	ENSP00000360669.3	A0A804CEY2

Frequencies

GnomAD3 genomes AF: 0.000460 AC: 70 AN: 152138 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00115 AC: 146 AN: 127166 AF XY: 0.00121

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000248

Gnomad ASJ exome AF: 0.0137

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000445

Gnomad OTH exome AF: 0.00126

GnomAD4 exome AF: 0.000790 AC: 239 AN: 302440 Hom.: 3 Cov.: 0 AF XY: 0.000784 AC XY: 135 AN XY: 172258

African (AFR) AF: 0.000117 AC: 1 AN: 8580

American (AMR) AF: 0.000294 AC: 8 AN: 27172

Ashkenazi Jewish (ASJ) AF: 0.0143 AC: 154 AN: 10736

East Asian (EAS) AF: 0.00 AC: 0 AN: 9190

South Asian (SAS) AF: 0.000151 AC: 9 AN: 59512

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12352

Middle Eastern (MID) AF: 0.00178 AC: 4 AN: 2244

European-Non Finnish (NFE) AF: 0.000290 AC: 46 AN: 158518

Other (OTH) AF: 0.00120 AC: 17 AN: 14136

GnomAD4 genome AF: 0.000460 AC: 70 AN: 152138 Hom.: 0 Cov.: 32 AF XY: 0.000431 AC XY: 32 AN XY: 74304

African (AFR) AF: 0.0000241 AC: 1 AN: 41438

American (AMR) AF: 0.000720 AC: 11 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68014

Other (OTH) AF: 0.000956 AC: 2 AN: 2092

Alfa AF: 0.00169 Hom.: 0

Bravo AF: 0.000578

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.8
DANN	Benign	0.66
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism

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: rs762515527; hg19: chr20-49492605;