20-50795157-C-T

Variant names:

• chr20-50795157-C-T
• rs1383293619
• NM_198799.4:c.74C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198799.4(BCAS4):​c.74C>T​(p.Pro25Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,116 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P25R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BCAS4 NM_198799.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14423314).

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.74C>T	p.Pro25Leu	missense	Exon 1 of 5	NP_942094.3	A0A804CEY2
	BCAS4	NM_017843.4		c.164C>T	p.Pro55Leu	missense	Exon 1 of 6	NP_060313.3	Q8TDM0-1
	BCAS4	NM_001010974.2		c.164C>T	p.Pro55Leu	missense	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.74C>T	p.Pro25Leu	missense	Exon 1 of 5	ENSP00000360669.3	A0A804CEY2
	BCAS4	ENST00000358791.9	TSL:1	c.164C>T	p.Pro55Leu	missense	Exon 1 of 6	ENSP00000351642.5	Q8TDM0-1
	BCAS4	ENST00000609336.5	TSL:1	c.74C>T	p.Pro25Leu	missense	Exon 1 of 6	ENSP00000477167.1	A0A0C4DGS6

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152116 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1310208 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 646374

African (AFR) AF: 0.00 AC: 0 AN: 27482

American (AMR) AF: 0.00 AC: 0 AN: 30532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23056

East Asian (EAS) AF: 0.00 AC: 0 AN: 29776

South Asian (SAS) AF: 0.00 AC: 0 AN: 70962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5180

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1034862

Other (OTH) AF: 0.00 AC: 0 AN: 53746

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152116 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74304

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0057	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.85	D
M_CAP	Pathogenic	0.35	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.5
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.10
Sift	Benign	0.16	T
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.15
MutPred		0.32		Loss of helix (P = 0.0104)
MVP		0.37
MPC		0.86
ClinPred		0.99	D
GERP RS		4.8
PromoterAI		0.033	Neutral
Varity_R		0.24
gMVP		0.11
Mutation Taster		=93/7	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: rs1383293619; hg19: chr20-49411694;