20-50795000-C-G

Variant names:

• chr20-50795000-C-G
• ENST00000358791.9:c.7C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017843.4(BCAS4):​c.7C>G​(p.Arg3Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000849 in 1,177,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: BCAS4 NM_017843.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.580

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06655201).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAS4	NM_198799.4	c.-84C>G		upstream_gene_variant		ENST00000371608.8	NP_942094.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAS4	ENST00000371608.8	c.-84C>G		upstream_gene_variant		1	NM_198799.4	ENSP00000360669.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.49e-7 AC: 1 AN: 1177650 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 572834

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000103

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 03, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.7C>G (p.R3G) alteration is located in exon 1 (coding exon 1) of the BCAS4 gene. This alteration results from a C to G substitution at nucleotide position 7, causing the arginine (R) at amino acid position 3 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.0020	T;.
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.067	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.90	L;L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.53	N;N
REVEL	Benign	0.032
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.012	D;D
Polyphen		0.0020	B;B
Vest4		0.10
MutPred		0.33		Loss of MoRF binding (P = 2e-04);Loss of MoRF binding (P = 2e-04);
MVP		0.15
MPC		0.35
ClinPred		0.17	T
GERP RS		0.87
Varity_R		0.088
gMVP		0.10

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-49411537;