rs4482462

Variant names:

• chr2-201157024-T-C
• rs4482462
• NM_003879.7:c.794-3408T>C

Variant summary

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

The NM_003879.7(CFLAR):​c.794-3408T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,152 control chromosomes in the GnomAD database, including 5,412 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 (5412 hom., cov: 32)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38
• Publications: 10 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=-1.12).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFLAR	NM_003879.7	c.794-3408T>C		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.794-3408T>C		intron_variant	Intron 8 of 9	1	NM_003879.7	ENSP00000312455.2

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37479 AN: 152036 Hom.: 5392 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.0400

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.247 AC: 37548 AN: 152152 Hom.: 5412 Cov.: 32 AF XY: 0.242 AC XY: 17991 AN XY: 74386

African (AFR) AF: 0.397 AC: 16480 AN: 41478

American (AMR) AF: 0.176 AC: 2690 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 971 AN: 3472

East Asian (EAS) AF: 0.0403 AC: 209 AN: 5192

South Asian (SAS) AF: 0.118 AC: 572 AN: 4830

European-Finnish (FIN) AF: 0.161 AC: 1705 AN: 10594

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14221 AN: 67988

Other (OTH) AF: 0.232 AC: 491 AN: 2114

Alfa AF: 0.259 Hom.: 1002

Bravo AF: 0.252

Asia WGS AF: 0.125 AC: 436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.053
DANN	Benign	0.30
PhyloP100		-2.4
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: rs4482462; hg19: chr2-202021747;