rs6728771

Positions:

• chr2-201127684-C-A

Variant summary

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

The NM_003879.7(CFLAR):​c.-137-2045C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,054 control chromosomes in the GnomAD database, including 9,634 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 0.30 (9634 hom., cov: 32)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.932

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFLAR	NM_003879.7	c.-137-2045C>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.-137-2045C>A		intron_variant		1	NM_003879.7	ENSP00000312455	P2

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45654 AN: 151936 Hom.: 9608 Cov.: 32

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.0123

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.301 AC: 45742 AN: 152054 Hom.: 9634 Cov.: 32 AF XY: 0.293 AC XY: 21791 AN XY: 74360

Gnomad4 AFR AF: 0.598

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.0123

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.269

Alfa AF: 0.224 Hom.: 4722

Bravo AF: 0.316

Asia WGS AF: 0.124 AC: 432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.49
DANN	Benign	0.40

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: rs6728771; hg19: chr2-201992407;