2-201150954-G-A

Position:

• chr2-201150954-G-A

Variant summary

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

The NM_003879.7(CFLAR):​c.793+1119G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,098 control chromosomes in the GnomAD database, including 3,311 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 0.19 (3311 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFLAR	NM_003879.7	c.793+1119G>A		intron_variant		ENST00000309955.8	NP_003870.4
CFLAR-AS1	NR_040030.1	n.563+144C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFLAR	ENST00000309955.8	c.793+1119G>A		intron_variant		1	NM_003879.7	ENSP00000312455	P2
CFLAR-AS1	ENST00000415011.6	n.594+144C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29524 AN: 151976 Hom.: 3309 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.0356

Gnomad SAS AF: 0.0577

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.192

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.194 AC: 29548 AN: 152094 Hom.: 3311 Cov.: 32 AF XY: 0.190 AC XY: 14135 AN XY: 74350

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.0359

Gnomad4 SAS AF: 0.0575

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.190

Alfa AF: 0.184 Hom.: 359

Bravo AF: 0.201

Asia WGS AF: 0.0660 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.84
DANN	Benign	0.39

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: rs13426823; hg19: chr2-202015677;