rs10931931

Positions:

• chr2-201129817-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.-49C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,573,690 control chromosomes in the GnomAD database, including 18,773 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 (3747 hom., cov: 31)
  • Exomes 𝑓: 0.14 (15026 hom.)
• Consequence: CFLAR NM_003879.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.766

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFLAR	NM_003879.7	c.-49C>T		5_prime_UTR_variant	2/10	ENST00000309955.8	NP_003870.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFLAR	ENST00000309955.8	c.-49C>T		5_prime_UTR_variant	2/10	1	NM_003879.7	ENSP00000312455	P2

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29309 AN: 151912 Hom.: 3741 Cov.: 31

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.00732

Gnomad SAS AF: 0.0441

Gnomad FIN AF: 0.0922

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.178

GnomAD3 exomes AF: 0.127 AC: 29885 AN: 234756 Hom.: 2689 AF XY: 0.123 AC XY: 15518 AN XY: 126624

Gnomad AFR exome AF: 0.373

Gnomad AMR exome AF: 0.0956

Gnomad ASJ exome AF: 0.149

Gnomad EAS exome AF: 0.00461

Gnomad SAS exome AF: 0.0511

Gnomad FIN exome AF: 0.0985

Gnomad NFE exome AF: 0.145

Gnomad OTH exome AF: 0.140

GnomAD4 exome AF: 0.137 AC: 194504 AN: 1421660 Hom.: 15026 Cov.: 27 AF XY: 0.134 AC XY: 94515 AN XY: 704718

Gnomad4 AFR exome AF: 0.362

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.00247

Gnomad4 SAS exome AF: 0.0520

Gnomad4 FIN exome AF: 0.0977

Gnomad4 NFE exome AF: 0.144

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.193 AC: 29347 AN: 152030 Hom.: 3747 Cov.: 31 AF XY: 0.187 AC XY: 13886 AN XY: 74326

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.00734

Gnomad4 SAS AF: 0.0439

Gnomad4 FIN AF: 0.0922

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.176

Alfa AF: 0.176 Hom.: 845

Bravo AF: 0.206

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.3
DANN	Benign	0.45
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0

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: rs10931931; hg19: chr2-201994540;