rs766673586

Variant names:

• chr19-47221899-C-G
• rs766673586
• NM_014417.5:c.485G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-47221899-C-G
• chr19-47221899-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014417.5(BBC3):​c.485G>C​(p.Arg162Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,438 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.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: BBC3 NM_014417.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.973

Genes affected

BBC3 (HGNC:17868): (BCL2 binding component 3) This gene encodes a member of the BCL-2 family of proteins. This family member belongs to the BH3-only pro-apoptotic subclass. The protein cooperates with direct activator proteins to induce mitochondrial outer membrane permeabilization and apoptosis. It can bind to anti-apoptotic Bcl-2 family members to induce mitochondrial dysfunction and caspase activation. Because of its pro-apoptotic role, this gene is a potential drug target for cancer therapy and for tissue injury. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35842335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBC3	NM_014417.5	c.485G>C	p.Arg162Pro	missense_variant	Exon 4 of 4	ENST00000439096.3	NP_055232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBC3	ENST00000439096.3	c.485G>C	p.Arg162Pro	missense_variant	Exon 4 of 4	1	NM_014417.5	ENSP00000395862.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000416 AC: 1 AN: 240402 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 130912

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000567

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454438 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723758

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.0052	T
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.31	.;T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-0.91	T
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Benign	0.17
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.91	P;D
Vest4		0.48
MutPred		0.27		.;Loss of MoRF binding (P = 6e-04);
MVP		0.79
ClinPred		0.46	T
GERP RS		3.6

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

LitVar

Other links and lift over

dbSNP: rs766673586; hg19: chr19-47725156;