rs1594

Positions:

• chr2-201160898-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003879.7(CFLAR):​c.1260A>G​(p.Pro420=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 1,610,572 control chromosomes in the GnomAD database, including 198,259 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 (17283 hom., cov: 28)
  • Exomes 𝑓: 0.49 (180976 hom.)
• Consequence: CFLAR NM_003879.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.78

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP7: Synonymous conserved (PhyloP=-2.78 with no splicing effect.
• 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	Protein	UniProt
CFLAR	NM_003879.7	c.1260A>G	p.Pro420=	synonymous_variant	9/10	ENST00000309955.8	NP_003870.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFLAR	ENST00000309955.8	c.1260A>G	p.Pro420=	synonymous_variant	9/10	1	NM_003879.7	ENSP00000312455	P2

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71816 AN: 151462 Hom.: 17262 Cov.: 28

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.468

GnomAD3 exomes AF: 0.446 AC: 111545 AN: 250140 Hom.: 25901 AF XY: 0.446 AC XY: 60400 AN XY: 135306

Gnomad AFR exome AF: 0.466

Gnomad AMR exome AF: 0.350

Gnomad ASJ exome AF: 0.526

Gnomad EAS exome AF: 0.253

Gnomad SAS exome AF: 0.367

Gnomad FIN exome AF: 0.483

Gnomad NFE exome AF: 0.511

Gnomad OTH exome AF: 0.459

GnomAD4 exome AF: 0.493 AC: 719053 AN: 1458992 Hom.: 180976 Cov.: 35 AF XY: 0.489 AC XY: 355208 AN XY: 725968

Gnomad4 AFR exome AF: 0.467

Gnomad4 AMR exome AF: 0.359

Gnomad4 ASJ exome AF: 0.531

Gnomad4 EAS exome AF: 0.219

Gnomad4 SAS exome AF: 0.369

Gnomad4 FIN exome AF: 0.481

Gnomad4 NFE exome AF: 0.519

Gnomad4 OTH exome AF: 0.482

GnomAD4 genome AF: 0.474 AC: 71877 AN: 151580 Hom.: 17283 Cov.: 28 AF XY: 0.467 AC XY: 34618 AN XY: 74056

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.474

Alfa AF: 0.503 Hom.: 30417

Bravo AF: 0.467

Asia WGS AF: 0.313 AC: 1090 AN: 3478

EpiCase AF: 0.499

EpiControl AF: 0.510

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.16
DANN	Benign	0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1594; hg19: chr2-202025621; COSMIC: COSV58579509; COSMIC: COSV58579509;