rs61289882

Positions:

• chr2-201150527-A-T

Variant summary

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

The ENST00000309955.8(CFLAR):​c.793+692A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,060 control chromosomes in the GnomAD database, including 5,680 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 (5679 hom., cov: 31)
  • Exomes 𝑓: 0.21 (1 hom.)
• Consequence: CFLAR ENST00000309955.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0810

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFLAR	NM_003879.7	c.793+692A>T		intron_variant		ENST00000309955.8	NP_003870.4
CFLAR-AS1	NR_040030.1	n.563+571T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFLAR	ENST00000309955.8	c.793+692A>T		intron_variant		1	NM_003879.7	ENSP00000312455	P2
CFLAR-AS1	ENST00000415011.6	n.594+571T>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38135 AN: 151856 Hom.: 5658 Cov.: 31

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.0399

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.232

GnomAD4 exome AF: 0.209 AC: 18 AN: 86 Hom.: 1 Cov.: 0 AF XY: 0.177 AC XY: 11 AN XY: 62

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.167

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.251 AC: 38205 AN: 151974 Hom.: 5679 Cov.: 31 AF XY: 0.246 AC XY: 18316 AN XY: 74312

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.0402

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.238

Alfa AF: 0.247 Hom.: 647

Bravo AF: 0.257

Asia WGS AF: 0.126 AC: 439 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	7.8
DANN	Benign	0.67

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: rs61289882; hg19: chr2-202015250;