NM_004050.5:c.*1703C>A

Variant names:

• chr14-23310668-C-A
• rs3210043
• NM_004050.5:c.*1703C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004050.5(BCL2L2):​c.*1703C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,136,690 control chromosomes in the GnomAD database, including 12,985 homozygotes. 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: 𝑓 0.11 (1198 hom., cov: 32)
  • Exomes 𝑓: 0.15 (11787 hom.)
• Consequence: BCL2L2 NM_004050.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 11 publications found

Genes affected

BCL2L2 (HGNC:995): (BCL2 like 2) This gene encodes a member of the BCL-2 protein family. The proteins of this family form hetero- or homodimers and act as anti- and pro-apoptotic regulators. Expression of this gene in cells has been shown to contribute to reduced cell apoptosis under cytotoxic conditions. Studies of the related gene in mice indicated a role in the survival of NGF- and BDNF-dependent neurons. Mutation and knockout studies of the mouse gene demonstrated an essential role in adult spermatogenesis. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring downstream PABPN1 (poly(A) binding protein, nuclear 1) gene. [provided by RefSeq, Dec 2010]

BCL2L2-PABPN1 (HGNC:42959): (BCL2L2-PABPN1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring BCL2L2 (BCL2-like 2) and PABPN1 (poly(A) binding protein, nuclear 1) genes on chromosome 14. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004050.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2L2	NM_004050.5	MANE Select	c.*1703C>A		3_prime_UTR	Exon 4 of 4	NP_004041.2
	BCL2L2	NM_001199839.2		c.*1703C>A		3_prime_UTR	Exon 4 of 4	NP_001186768.2
	BCL2L2-PABPN1	NM_001387340.1		c.549+1736C>A		intron	N/A	NP_001374269.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2L2	ENST00000250405.10	TSL:1 MANE Select	c.*1703C>A		3_prime_UTR	Exon 4 of 4	ENSP00000250405.6
	BCL2L2-PABPN1	ENST00000553781.5	TSL:2	c.432+2469C>A		intron	N/A	ENSP00000451320.1
	BCL2L2	ENST00000678311.1		c.*1703C>A		3_prime_UTR	Exon 4 of 4	ENSP00000504570.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16750 AN: 152034 Hom.: 1193 Cov.: 32

Gnomad AFR AF: 0.0313

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0623

Gnomad SAS AF: 0.0363

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.149 AC: 146979 AN: 984538 Hom.: 11787 Cov.: 32 AF XY: 0.147 AC XY: 68581 AN XY: 467886

African (AFR) AF: 0.0196 AC: 359 AN: 18312

American (AMR) AF: 0.121 AC: 794 AN: 6560

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 1262 AN: 8444

East Asian (EAS) AF: 0.0549 AC: 405 AN: 7382

South Asian (SAS) AF: 0.0370 AC: 1812 AN: 48992

European-Finnish (FIN) AF: 0.130 AC: 1074 AN: 8250

Middle Eastern (MID) AF: 0.121 AC: 262 AN: 2172

European-Non Finnish (NFE) AF: 0.161 AC: 136648 AN: 849798

Other (OTH) AF: 0.126 AC: 4363 AN: 34628

GnomAD4 genome AF: 0.110 AC: 16760 AN: 152152 Hom.: 1198 Cov.: 32 AF XY: 0.107 AC XY: 7991 AN XY: 74384

African (AFR) AF: 0.0312 AC: 1296 AN: 41512

American (AMR) AF: 0.124 AC: 1903 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 541 AN: 3468

East Asian (EAS) AF: 0.0624 AC: 323 AN: 5176

South Asian (SAS) AF: 0.0363 AC: 175 AN: 4822

European-Finnish (FIN) AF: 0.144 AC: 1526 AN: 10570

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10574 AN: 67996

Other (OTH) AF: 0.135 AC: 285 AN: 2110

Alfa AF: 0.143 Hom.: 2346

Bravo AF: 0.108

Asia WGS AF: 0.0610 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	15
DANN	Benign	0.89
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs3210043; hg19: chr14-23779877; COSMIC: COSV105859652;