22-17728439-T-C

Variant names:

• chr22-17728439-T-C
• rs9967
• ENST00000399777.2:n.*1861T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000399777.2(BCL2L13):​n.*1861T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 152,132 control chromosomes in the GnomAD database, including 16,545 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 0.45 (16545 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: BCL2L13 ENST00000399777.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 18 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2L13	NM_015367.4	c.*905T>C		3_prime_UTR_variant	Exon 7 of 7	ENST00000317582.10	NP_056182.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL2L13	ENST00000317582.10	c.*905T>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_015367.4	ENSP00000318883.5

Frequencies

GnomAD3 genomes AF: 0.454 AC: 69007 AN: 152006 Hom.: 16542 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.459

GnomAD4 exome AF: 0.250 AC: 2 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.454 AC: 69041 AN: 152124 Hom.: 16545 Cov.: 32 AF XY: 0.462 AC XY: 34326 AN XY: 74358

African (AFR) AF: 0.359 AC: 14908 AN: 41490

American (AMR) AF: 0.563 AC: 8603 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1586 AN: 3472

East Asian (EAS) AF: 0.812 AC: 4206 AN: 5178

South Asian (SAS) AF: 0.591 AC: 2853 AN: 4824

European-Finnish (FIN) AF: 0.462 AC: 4895 AN: 10584

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30361 AN: 67976

Other (OTH) AF: 0.462 AC: 975 AN: 2110

Alfa AF: 0.458 Hom.: 24177

Bravo AF: 0.462

Asia WGS AF: 0.667 AC: 2315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.47
DANN	Benign	0.52
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: rs9967; hg19: chr22-18211205;