NM_003879.7:c.794-3660C>T

Variant names:

• chr2-201156772-C-T
• rs2041766
• NM_003879.7:c.794-3660C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003879.7(CFLAR):​c.794-3660C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 144,200 control chromosomes in the GnomAD database, including 4,853 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 (4853 hom., cov: 28)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFLAR	NM_003879.7	c.794-3660C>T		intron_variant	Intron 8 of 9	ENST00000309955.8	NP_003870.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFLAR	ENST00000309955.8	c.794-3660C>T		intron_variant	Intron 8 of 9	1	NM_003879.7	ENSP00000312455.2

Frequencies

GnomAD3 genomes AF: 0.248 AC: 35791 AN: 144068 Hom.: 4835 Cov.: 28

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.0490

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.249 AC: 35857 AN: 144200 Hom.: 4853 Cov.: 28 AF XY: 0.245 AC XY: 17191 AN XY: 70032

African (AFR) AF: 0.373 AC: 15013 AN: 40232

American (AMR) AF: 0.183 AC: 2616 AN: 14282

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 966 AN: 3386

East Asian (EAS) AF: 0.0493 AC: 204 AN: 4140

South Asian (SAS) AF: 0.138 AC: 558 AN: 4058

European-Finnish (FIN) AF: 0.181 AC: 1664 AN: 9214

Middle Eastern (MID) AF: 0.190 AC: 54 AN: 284

European-Non Finnish (NFE) AF: 0.216 AC: 14161 AN: 65706

Other (OTH) AF: 0.232 AC: 468 AN: 2016

Alfa AF: 0.225 Hom.: 1396

Bravo AF: 0.242

Asia WGS AF: 0.120 AC: 420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.9
DANN	Benign	0.33
PhyloP100		-0.046
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2041766; hg19: chr2-202021495;