rs68044560

Variant names:

• chr2-201152357-T-C
• rs68044560
• NM_003879.7:c.793+2522T>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.793+2522T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,954 control chromosomes in the GnomAD database, including 5,656 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 (5656 hom., cov: 31)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 6 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003879.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFLAR	NM_003879.7	MANE Select	c.793+2522T>C		intron	N/A	NP_003870.4
	CFLAR	NM_001127183.4		c.793+2522T>C		intron	N/A	NP_001120655.1
	CFLAR	NM_001308042.3		c.793+2522T>C		intron	N/A	NP_001294971.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFLAR	ENST00000309955.8	TSL:1 MANE Select	c.793+2522T>C		intron	N/A	ENSP00000312455.2
	CFLAR	ENST00000423241.6	TSL:1	c.793+2522T>C		intron	N/A	ENSP00000399420.2
	CFLAR	ENST00000457277.5	TSL:1	c.793+2522T>C		intron	N/A	ENSP00000411535.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38068 AN: 151836 Hom.: 5635 Cov.: 31

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.0400

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.251 AC: 38137 AN: 151954 Hom.: 5656 Cov.: 31 AF XY: 0.246 AC XY: 18269 AN XY: 74276

African (AFR) AF: 0.412 AC: 17059 AN: 41394

American (AMR) AF: 0.177 AC: 2694 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 969 AN: 3468

East Asian (EAS) AF: 0.0403 AC: 209 AN: 5188

South Asian (SAS) AF: 0.118 AC: 570 AN: 4816

European-Finnish (FIN) AF: 0.161 AC: 1702 AN: 10584

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14221 AN: 67968

Other (OTH) AF: 0.237 AC: 500 AN: 2110

Alfa AF: 0.247 Hom.: 646

Bravo AF: 0.257

Asia WGS AF: 0.125 AC: 436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.34
PhyloP100		-1.1
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: rs68044560; hg19: chr2-202017080;