ENST00000449228.5:c.708C>T

Variant names:

• chr19-47221779-G-A
• rs202031784
• ENST00000449228.5:c.708C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The ENST00000449228.5(BBC3):​c.708C>T​(p.Asp236Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00815 in 1,608,400 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0065 (10 hom., cov: 31)
  • Exomes 𝑓: 0.0083 (63 hom.)
• Consequence: BBC3 ENST00000449228.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.335
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 19-47221779-G-A is Benign according to our data. Variant chr19-47221779-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 770466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.335 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000449228.5. 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
	BBC3	NM_014417.5	MANE Select	c.*23C>T		3_prime_UTR	Exon 4 of 4	NP_055232.1	Q9BXH1-1
	BBC3	NM_001127240.3		c.708C>T	p.Asp236Asp	synonymous	Exon 4 of 4	NP_001120712.1	Q96PG8-2
	BBC3	NM_001127242.3		c.228C>T	p.Asp76Asp	synonymous	Exon 2 of 2	NP_001120714.1	Q96PG8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBC3	ENST00000449228.5	TSL:1	c.708C>T	p.Asp236Asp	synonymous	Exon 4 of 4	ENSP00000404503.1	Q96PG8-2
	BBC3	ENST00000300880.11	TSL:1	c.228C>T	p.Asp76Asp	synonymous	Exon 2 of 2	ENSP00000300880.7	Q96PG8-1
	BBC3	ENST00000439096.3	TSL:1 MANE Select	c.*23C>T		3_prime_UTR	Exon 4 of 4	ENSP00000395862.2	Q9BXH1-1

Frequencies

GnomAD3 genomes AF: 0.00647 AC: 984 AN: 152124 Hom.: 10 Cov.: 31

Gnomad AFR AF: 0.00179

Gnomad AMI AF: 0.0813

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.00574

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0100

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00572 AC: 1372 AN: 239888 AF XY: 0.00591

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.00174

Gnomad ASJ exome AF: 0.00897

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00614

Gnomad NFE exome AF: 0.00881

Gnomad OTH exome AF: 0.00634

GnomAD4 exome AF: 0.00832 AC: 12121 AN: 1456158 Hom.: 63 Cov.: 31 AF XY: 0.00830 AC XY: 6014 AN XY: 724660

African (AFR) AF: 0.00133 AC: 44 AN: 33084

American (AMR) AF: 0.00199 AC: 85 AN: 42678

Ashkenazi Jewish (ASJ) AF: 0.00909 AC: 235 AN: 25864

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.00311 AC: 267 AN: 85858

European-Finnish (FIN) AF: 0.00615 AC: 326 AN: 53034

Middle Eastern (MID) AF: 0.00357 AC: 20 AN: 5596

European-Non Finnish (NFE) AF: 0.00965 AC: 10715 AN: 1110338

Other (OTH) AF: 0.00714 AC: 429 AN: 60064

GnomAD4 genome AF: 0.00646 AC: 983 AN: 152242 Hom.: 10 Cov.: 31 AF XY: 0.00601 AC XY: 447 AN XY: 74430

African (AFR) AF: 0.00178 AC: 74 AN: 41550

American (AMR) AF: 0.00229 AC: 35 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00353 AC: 17 AN: 4822

European-Finnish (FIN) AF: 0.00574 AC: 61 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0100 AC: 681 AN: 67994

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00667 Hom.: 4

Bravo AF: 0.00618

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00894

EpiControl AF: 0.00797

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.56
PhyloP100		0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=98/2	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: rs202031784; hg19: chr19-47725036;