rs719126

Positions:

• chr2-201153107-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.793+3272C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0385 in 152,298 control chromosomes in the GnomAD database, including 140 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 0.038 (140 hom., cov: 32)
  • Exomes 𝑓: 0.020 (0 hom.)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFLAR	NM_003879.7	c.793+3272C>T		intron_variant		ENST00000309955.8	NP_003870.4
CFLAR-AS1	NR_040030.1	n.401+204G>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+3272C>T		intron_variant		1	NM_003879.7	ENSP00000312455	P2
CFLAR-AS1	ENST00000415011.6	n.432+204G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0383 AC: 5833 AN: 152130 Hom.: 132 Cov.: 32

Gnomad AFR AF: 0.0463

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0217

Gnomad ASJ AF: 0.0896

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0611

Gnomad FIN AF: 0.0246

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0383

Gnomad OTH AF: 0.0287

GnomAD4 exome AF: 0.0200 AC: 1 AN: 50 Hom.: 0 Cov.: 0 AF XY: 0.0294 AC XY: 1 AN XY: 34

Gnomad4 AMR exome AF: 0.00

Gnomad4 NFE exome AF: 0.0238

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0385 AC: 5856 AN: 152248 Hom.: 140 Cov.: 32 AF XY: 0.0378 AC XY: 2814 AN XY: 74436

Gnomad4 AFR AF: 0.0464

Gnomad4 AMR AF: 0.0217

Gnomad4 ASJ AF: 0.0896

Gnomad4 EAS AF: 0.00386

Gnomad4 SAS AF: 0.0605

Gnomad4 FIN AF: 0.0246

Gnomad4 NFE AF: 0.0383

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.0414 Hom.: 15

Bravo AF: 0.0359

Asia WGS AF: 0.0510 AC: 177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.61

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: rs719126; hg19: chr2-202017830;