rs6712963

Positions:

• chr2-201117970-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.-138+1489G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 151,812 control chromosomes in the GnomAD database, including 1,999 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 0.15 (1999 hom., cov: 31)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140

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 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFLAR	NM_003879.7	c.-138+1489G>A		intron_variant		ENST00000309955.8	NP_003870.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFLAR	ENST00000309955.8	c.-138+1489G>A		intron_variant		1	NM_003879.7	ENSP00000312455.2

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23232 AN: 151696 Hom.: 1995 Cov.: 31

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.00735

Gnomad SAS AF: 0.0435

Gnomad FIN AF: 0.0949

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.153 AC: 23256 AN: 151812 Hom.: 1999 Cov.: 31 AF XY: 0.148 AC XY: 10985 AN XY: 74206

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.00736

Gnomad4 SAS AF: 0.0434

Gnomad4 FIN AF: 0.0949

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.147

Alfa AF: 0.161 Hom.: 271

Bravo AF: 0.160

Asia WGS AF: 0.0440 AC: 155 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	5.0
DANN	Benign	0.77

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: rs6712963; hg19: chr2-201982693;