2-201149515-G-C

Position:

• chr2-201149515-G-C

Variant summary

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

The NM_003879.7(CFLAR):​c.712-239G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 365,116 control chromosomes in the GnomAD database, including 9,881 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 (5667 hom., cov: 32)
  • Exomes 𝑓: 0.18 (4214 hom.)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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=-0.87).
• 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	UniProt
CFLAR	NM_003879.7	c.712-239G>C		intron_variant		ENST00000309955.8
CFLAR-AS1	NR_040030.1	n.670+139C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFLAR	ENST00000309955.8	c.712-239G>C		intron_variant		1	NM_003879.7	P2
CFLAR-AS1	ENST00000415011.6	n.701+139C>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38145 AN: 151980 Hom.: 5646 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.0402

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.182 AC: 38685 AN: 213018 Hom.: 4214 Cov.: 0 AF XY: 0.179 AC XY: 20134 AN XY: 112396

Gnomad4 AFR exome AF: 0.400

Gnomad4 AMR exome AF: 0.139

Gnomad4 ASJ exome AF: 0.254

Gnomad4 EAS exome AF: 0.0159

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.157

Gnomad4 NFE exome AF: 0.199

Gnomad4 OTH exome AF: 0.199

GnomAD4 genome AF: 0.251 AC: 38214 AN: 152098 Hom.: 5667 Cov.: 32 AF XY: 0.246 AC XY: 18317 AN XY: 74346

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.0405

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.237

Alfa AF: 0.136 Hom.: 245

Bravo AF: 0.257

Asia WGS AF: 0.125 AC: 438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.22
DANN	Benign	0.53

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: rs12721505; hg19: chr2-202014238;