rs73045343

Positions:

• chr2-201152685-G-A

Variant summary

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

The NM_003879.7(CFLAR):​c.793+2850G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,142 control chromosomes in the GnomAD database, including 2,979 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 0.18 (2978 hom., cov: 32)
  • Exomes 𝑓: 0.15 (1 hom.)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78

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]

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=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFLAR	NM_003879.7	c.793+2850G>A		intron_variant		ENST00000309955.8
CFLAR-AS1	NR_040030.1	n.401+626C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFLAR	ENST00000309955.8	c.793+2850G>A		intron_variant		1	NM_003879.7	P2
CFLAR-AS1	ENST00000415011.6	n.432+626C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27612 AN: 151976 Hom.: 2977 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.0353

Gnomad SAS AF: 0.0454

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.146 AC: 7 AN: 48 Hom.: 1 AF XY: 0.184 AC XY: 7 AN XY: 38

Gnomad4 AFR exome AF: 0.167

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.182 AC: 27626 AN: 152094 Hom.: 2978 Cov.: 32 AF XY: 0.178 AC XY: 13245 AN XY: 74380

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.0356

Gnomad4 SAS AF: 0.0452

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.176

Alfa AF: 0.172 Hom.: 438

Bravo AF: 0.190

Asia WGS AF: 0.0590 AC: 208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	11
DANN	Benign	0.81

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: rs73045343; hg19: chr2-202017408;