rs12104442

Positions:

• chr2-201149233-T-C

Variant summary

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

The NM_003879.7(CFLAR):​c.711+181T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 516,362 control chromosomes in the GnomAD database, including 12,508 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 0.24 (5174 hom., cov: 32)
  • Exomes 𝑓: 0.19 (7334 hom.)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFLAR	NM_003879.7	c.711+181T>C		intron_variant		ENST00000309955.8	NP_003870.4
CFLAR-AS1	NR_040030.1	n.671-33A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFLAR	ENST00000309955.8	c.711+181T>C		intron_variant		1	NM_003879.7	ENSP00000312455	P2
CFLAR-AS1	ENST00000415011.6	n.702-33A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36864 AN: 151986 Hom.: 5155 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.0395

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.187 AC: 68166 AN: 364258 Hom.: 7334 Cov.: 4 AF XY: 0.185 AC XY: 35831 AN XY: 193306

Gnomad4 AFR exome AF: 0.385

Gnomad4 AMR exome AF: 0.144

Gnomad4 ASJ exome AF: 0.259

Gnomad4 EAS exome AF: 0.0195

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.208

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.243 AC: 36931 AN: 152104 Hom.: 5174 Cov.: 32 AF XY: 0.238 AC XY: 17714 AN XY: 74356

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.0398

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.232

Alfa AF: 0.224 Hom.: 1389

Bravo AF: 0.248

Asia WGS AF: 0.121 AC: 423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.5
DANN	Benign	0.66

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: rs12104442; hg19: chr2-202013956;