rs12620435

Positions:

• chr2-201131056-A-G

Variant summary

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

The NM_003879.7(CFLAR):​c.281+910A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,172 control chromosomes in the GnomAD database, including 921 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 0.10 (921 hom., cov: 31)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFLAR	NM_003879.7	c.281+910A>G		intron_variant		ENST00000309955.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFLAR	ENST00000309955.8	c.281+910A>G		intron_variant		1	NM_003879.7	P2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15755 AN: 152054 Hom.: 916 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0910

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0818

Gnomad FIN AF: 0.0684

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0900

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.104 AC: 15775 AN: 152172 Hom.: 921 Cov.: 31 AF XY: 0.101 AC XY: 7528 AN XY: 74402

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0908

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.0810

Gnomad4 FIN AF: 0.0684

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.0967

Alfa AF: 0.112 Hom.: 1136

Bravo AF: 0.104

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.55

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: rs12620435; hg19: chr2-201995779;