chr2-201157804-G-C

Position:

• chr2-201157804-G-C

Variant summary

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

The NM_003879.7(CFLAR):​c.794-2628G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 152,090 control chromosomes in the GnomAD database, including 17,197 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 0.47 (17197 hom., cov: 33)
  • Exomes 𝑓: 0.20 (0 hom.)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFLAR	NM_003879.7	c.794-2628G>C		intron_variant		ENST00000309955.8
CFLAR-AS1	NR_040030.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFLAR	ENST00000309955.8	c.794-2628G>C		intron_variant		1	NM_003879.7	P2
CFLAR-AS1	ENST00000415011.6	n.20C>G		non_coding_transcript_exon_variant	1/7	1

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71620 AN: 151962 Hom.: 17175 Cov.: 33

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.463

GnomAD4 exome AF: 0.200 AC: 2 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.200 AC XY: 2 AN XY: 10

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.471 AC: 71684 AN: 152080 Hom.: 17197 Cov.: 33 AF XY: 0.465 AC XY: 34524 AN XY: 74324

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.469

Alfa AF: 0.380 Hom.: 1070

Bravo AF: 0.464

Asia WGS AF: 0.314 AC: 1094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.7
DANN	Benign	0.47

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: rs2268791; hg19: chr2-202022527;