20-50795158-C-G

Variant names:

• chr20-50795158-C-G
• rs777462572
• NM_198799.4:c.75C>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_198799.4(BCAS4):​c.75C>G​(p.Pro25Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000513 in 1,461,598 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P25P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000050 (0 hom.)
• Consequence: BCAS4 NM_198799.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98
• Publications: 0 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]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.079).
• BP7: Synonymous conserved (PhyloP=-2.98 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198799.4. 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.75C>G	p.Pro25Pro	synonymous	Exon 1 of 5	NP_942094.3	A0A804CEY2
	BCAS4	NM_017843.4		c.165C>G	p.Pro55Pro	synonymous	Exon 1 of 6	NP_060313.3	Q8TDM0-1
	BCAS4	NM_001010974.2		c.165C>G	p.Pro55Pro	synonymous	Exon 1 of 4	NP_001010974.1	Q8TDM0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAS4	ENST00000371608.8	TSL:1 MANE Select	c.75C>G	p.Pro25Pro	synonymous	Exon 1 of 5	ENSP00000360669.3	A0A804CEY2
	BCAS4	ENST00000358791.9	TSL:1	c.165C>G	p.Pro55Pro	synonymous	Exon 1 of 6	ENSP00000351642.5	Q8TDM0-1
	BCAS4	ENST00000609336.5	TSL:1	c.75C>G	p.Pro25Pro	synonymous	Exon 1 of 6	ENSP00000477167.1	A0A0C4DGS6

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152118 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000217 AC: 21 AN: 96678 AF XY: 0.000260

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00255

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000551

Gnomad OTH exome AF: 0.000348

GnomAD4 exome AF: 0.0000504 AC: 66 AN: 1309480 Hom.: 0 Cov.: 31 AF XY: 0.0000619 AC XY: 40 AN XY: 645976

African (AFR) AF: 0.00 AC: 0 AN: 27452

American (AMR) AF: 0.00 AC: 0 AN: 30486

Ashkenazi Jewish (ASJ) AF: 0.00209 AC: 48 AN: 23008

East Asian (EAS) AF: 0.00 AC: 0 AN: 29736

South Asian (SAS) AF: 0.00 AC: 0 AN: 70858

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5176

European-Non Finnish (NFE) AF: 0.0000116 AC: 12 AN: 1034502

Other (OTH) AF: 0.000112 AC: 6 AN: 53700

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152118 Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6 AN XY: 74300

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67992

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.000269 Hom.: 1

Bravo AF: 0.0000793

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.9
DANN	Benign	0.71
PhyloP100		-3.0
PromoterAI		0.085	Neutral

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: rs777462572; hg19: chr20-49411695;