22-17727938-G-C

Variant names:

• chr22-17727938-G-C
• rs2587100
• ENST00000399777.2:n.*1360G>C

Variant summary

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

The ENST00000399777.2(BCL2L13):​n.*1360G>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 0.391 in 209,184 control chromosomes in the GnomAD database, including 17,465 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 0.41 (13525 hom., cov: 33)
  • Exomes 𝑓: 0.35 (3940 hom.)
• Consequence: BCL2L13 ENST00000399777.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186
• Publications: 13 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2L13	NM_015367.4	c.*404G>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.*404G>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_015367.4	ENSP00000318883.5

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61799 AN: 151930 Hom.: 13503 Cov.: 33

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.374

GnomAD4 exome AF: 0.350 AC: 20005 AN: 57136 Hom.: 3940 Cov.: 0 AF XY: 0.343 AC XY: 10117 AN XY: 29526

African (AFR) AF: 0.542 AC: 1684 AN: 3106

American (AMR) AF: 0.267 AC: 1118 AN: 4186

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 505 AN: 1512

East Asian (EAS) AF: 0.194 AC: 902 AN: 4646

South Asian (SAS) AF: 0.218 AC: 1225 AN: 5632

European-Finnish (FIN) AF: 0.333 AC: 513 AN: 1540

Middle Eastern (MID) AF: 0.282 AC: 53 AN: 188

European-Non Finnish (NFE) AF: 0.387 AC: 12960 AN: 33446

Other (OTH) AF: 0.363 AC: 1045 AN: 2880

GnomAD4 genome AF: 0.407 AC: 61864 AN: 152048 Hom.: 13525 Cov.: 33 AF XY: 0.396 AC XY: 29466 AN XY: 74320

African (AFR) AF: 0.535 AC: 22199 AN: 41466

American (AMR) AF: 0.298 AC: 4552 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1286 AN: 3468

East Asian (EAS) AF: 0.199 AC: 1028 AN: 5166

South Asian (SAS) AF: 0.203 AC: 979 AN: 4820

European-Finnish (FIN) AF: 0.347 AC: 3658 AN: 10556

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.397 AC: 26978 AN: 67970

Other (OTH) AF: 0.371 AC: 784 AN: 2112

Alfa AF: 0.287 Hom.: 761

Bravo AF: 0.409

Asia WGS AF: 0.225 AC: 786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.9
DANN	Benign	0.57
PhyloP100		0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2587100; hg19: chr22-18210704;