rs2518142

Positions:

• chr2-201160408-G-A
• chr2-201160408-G-C
• chr2-201160408-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003879.7(CFLAR):​c.794-24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 1,602,208 control chromosomes in the GnomAD database, including 638,173 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.88 (59435 hom., cov: 30)
  • Exomes 𝑓: 0.89 (578738 hom.)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13

Genes affected

CFLAR (HGNC:1876): (CASP8 and FADD like apoptosis regulator) The protein encoded by this gene is a regulator of apoptosis and is structurally similar to caspase-8. However, the encoded protein lacks caspase activity and appears to be itself cleaved into two peptides by caspase-8. Several transcript variants encoding different isoforms have been found for this gene, and partial evidence for several more variants exists. [provided by RefSeq, Feb 2011]

CFLAR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFLAR	NM_003879.7	c.794-24G>A		intron_variant		ENST00000309955.8	NP_003870.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFLAR	ENST00000309955.8	c.794-24G>A		intron_variant		1	NM_003879.7	ENSP00000312455.2

Frequencies

GnomAD3 genomes AF: 0.882 AC: 134086 AN: 151976 Hom.: 59392 Cov.: 30

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.867

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.970

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.910

Gnomad OTH AF: 0.874

GnomAD3 exomes AF: 0.870 AC: 213615 AN: 245416 Hom.: 93766 AF XY: 0.865 AC XY: 115027 AN XY: 133008

Gnomad AFR exome AF: 0.840

Gnomad AMR exome AF: 0.840

Gnomad ASJ exome AF: 0.934

Gnomad EAS exome AF: 0.872

Gnomad SAS exome AF: 0.698

Gnomad FIN exome AF: 0.964

Gnomad NFE exome AF: 0.909

Gnomad OTH exome AF: 0.886

GnomAD4 exome AF: 0.891 AC: 1292656 AN: 1450114 Hom.: 578738 Cov.: 41 AF XY: 0.886 AC XY: 638864 AN XY: 720878

Gnomad4 AFR exome AF: 0.831

Gnomad4 AMR exome AF: 0.845

Gnomad4 ASJ exome AF: 0.936

Gnomad4 EAS exome AF: 0.819

Gnomad4 SAS exome AF: 0.704

Gnomad4 FIN exome AF: 0.961

Gnomad4 NFE exome AF: 0.909

Gnomad4 OTH exome AF: 0.886

GnomAD4 genome AF: 0.882 AC: 134186 AN: 152094 Hom.: 59435 Cov.: 30 AF XY: 0.880 AC XY: 65410 AN XY: 74362

Gnomad4 AFR AF: 0.843

Gnomad4 AMR AF: 0.866

Gnomad4 ASJ AF: 0.933

Gnomad4 EAS AF: 0.856

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.970

Gnomad4 NFE AF: 0.910

Gnomad4 OTH AF: 0.875

Alfa AF: 0.902 Hom.: 105708

Bravo AF: 0.874

Asia WGS AF: 0.752 AC: 2618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.070
DANN	Benign	0.43
BranchPoint Hunter		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs2518142; hg19: chr2-202025131;