rs4487072

Positions:

• chr2-201143575-C-T

Variant summary

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

The NM_003879.7(CFLAR):​c.607-1803C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 151,992 control chromosomes in the GnomAD database, including 5,187 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 0.24 (5187 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.608

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFLAR	NM_003879.7	c.607-1803C>T		intron_variant		ENST00000309955.8	NP_003870.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFLAR	ENST00000309955.8	c.607-1803C>T		intron_variant		1	NM_003879.7	ENSP00000312455.2

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36895 AN: 151874 Hom.: 5168 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.0397

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.225

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.243 AC: 36963 AN: 151992 Hom.: 5187 Cov.: 32 AF XY: 0.239 AC XY: 17727 AN XY: 74278

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.0399

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.231

Alfa AF: 0.213 Hom.: 1820

Bravo AF: 0.248

Asia WGS AF: 0.121 AC: 422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.18
DANN	Benign	0.56

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: rs4487072; hg19: chr2-202008298;