rs2041766

chr2-201156772-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.794-3660C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 144,200 control chromosomes in the GnomAD database, including 4,853 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 0.25 (4853 hom., cov: 28)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460

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:14437): (CFLAR antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -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 = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFLAR	NM_003879.7	c.794-3660C>T		intron_variant		ENST00000309955.8
CFLAR-AS1	NR_040030.1	n.38+983G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFLAR	ENST00000309955.8	c.794-3660C>T		intron_variant		1	NM_003879.7	P2
CFLAR-AS1	ENST00000415011.6	n.69+983G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 35791 AN: 144068 Hom.: 4835 Cov.: 28

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.0490

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.226

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.249 AC: 35857 AN: 144200 Hom.: 4853 Cov.: 28 AF XY: 0.245 AC XY: 17191 AN XY: 70032

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.0493

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.232

Alfa AF: 0.240 Hom.: 759

Bravo AF: 0.242

Asia WGS AF: 0.120 AC: 420 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	5.9
Dann	Benign	0.33

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: rs2041766; hg19: chr2-202021495;