22-17727643-T-G

Variant names:

• chr22-17727643-T-G
• rs725768
• NM_015367.4:c.*109T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_015367.4(BCL2L13):​c.*109T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 1,452,268 control chromosomes in the GnomAD database, including 978 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 0.025 (73 hom., cov: 33)
  • Exomes 𝑓: 0.035 (905 hom.)
• Consequence: BCL2L13 NM_015367.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520
• Publications: 8 publications found

Genes affected

BCL2L13 (HGNC:17164): (BCL2 like 13) This gene encodes a mitochondrially-localized protein with conserved B-cell lymphoma 2 homology motifs. Overexpression of the encoded protein results in apoptosis. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0254 (3875/152306) while in subpopulation NFE AF = 0.0387 (2634/68016). AF 95% confidence interval is 0.0375. There are 73 homozygotes in GnomAd4. There are 1889 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 73 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015367.4. 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
	BCL2L13	NM_015367.4	MANE Select	c.*109T>G		3_prime_UTR	Exon 7 of 7	NP_056182.2
	BCL2L13	NM_001270726.1		c.*109T>G		3_prime_UTR	Exon 6 of 6	NP_001257655.1
	BCL2L13	NM_001270727.1		c.*109T>G		3_prime_UTR	Exon 5 of 5	NP_001257656.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2L13	ENST00000317582.10	TSL:1 MANE Select	c.*109T>G		3_prime_UTR	Exon 7 of 7	ENSP00000318883.5
	BCL2L13	ENST00000355028.4	TSL:1	c.*837T>G		3_prime_UTR	Exon 5 of 5	ENSP00000347133.3
	BCL2L13	ENST00000399777.2	TSL:1	n.*1065T>G		non_coding_transcript_exon	Exon 6 of 6	ENSP00000382677.2

Frequencies

GnomAD3 genomes AF: 0.0255 AC: 3875 AN: 152188 Hom.: 73 Cov.: 33

Gnomad AFR AF: 0.00678

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0187

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00455

Gnomad FIN AF: 0.0475

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0387

Gnomad OTH AF: 0.0229

GnomAD4 exome AF: 0.0349 AC: 45384 AN: 1299962 Hom.: 905 Cov.: 20 AF XY: 0.0338 AC XY: 21733 AN XY: 642812

African (AFR) AF: 0.00498 AC: 149 AN: 29916

American (AMR) AF: 0.0121 AC: 417 AN: 34400

Ashkenazi Jewish (ASJ) AF: 0.0204 AC: 424 AN: 20794

East Asian (EAS) AF: 0.0000260 AC: 1 AN: 38462

South Asian (SAS) AF: 0.00470 AC: 342 AN: 72808

European-Finnish (FIN) AF: 0.0457 AC: 1660 AN: 36356

Middle Eastern (MID) AF: 0.00665 AC: 27 AN: 4060

European-Non Finnish (NFE) AF: 0.0403 AC: 40694 AN: 1008680

Other (OTH) AF: 0.0307 AC: 1670 AN: 54486

GnomAD4 genome AF: 0.0254 AC: 3875 AN: 152306 Hom.: 73 Cov.: 33 AF XY: 0.0254 AC XY: 1889 AN XY: 74490

African (AFR) AF: 0.00676 AC: 281 AN: 41562

American (AMR) AF: 0.0187 AC: 286 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00455 AC: 22 AN: 4830

European-Finnish (FIN) AF: 0.0475 AC: 505 AN: 10624

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0387 AC: 2634 AN: 68016

Other (OTH) AF: 0.0222 AC: 47 AN: 2114

Alfa AF: 0.0328 Hom.: 248

Bravo AF: 0.0222

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.8
DANN	Benign	0.75
PhyloP100		0.052
Mutation Taster		=100/0	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: rs725768; hg19: chr22-18210409;