rs58886660

Variant names:

• chr2-201134560-A-G
• rs58886660
• NM_003879.7:c.388-1412A>G

Variant summary

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

The NM_003879.7(CFLAR):​c.388-1412A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 151,624 control chromosomes in the GnomAD database, including 5,530 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 (5530 hom., cov: 31)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 7 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 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.388-1412A>G		intron	N/A	NP_003870.4
	CFLAR	NM_001127183.4		c.388-1412A>G		intron	N/A	NP_001120655.1
	CFLAR	NM_001308042.3		c.388-1412A>G		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.388-1412A>G		intron	N/A	ENSP00000312455.2
	CFLAR	ENST00000423241.6	TSL:1	c.388-1412A>G		intron	N/A	ENSP00000399420.2
	CFLAR	ENST00000457277.5	TSL:1	c.388-1412A>G		intron	N/A	ENSP00000411535.1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37146 AN: 151504 Hom.: 5509 Cov.: 31

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.0124

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.245 AC: 37216 AN: 151624 Hom.: 5530 Cov.: 31 AF XY: 0.239 AC XY: 17749 AN XY: 74114

African (AFR) AF: 0.416 AC: 17127 AN: 41220

American (AMR) AF: 0.175 AC: 2666 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 960 AN: 3470

East Asian (EAS) AF: 0.0124 AC: 64 AN: 5168

South Asian (SAS) AF: 0.117 AC: 563 AN: 4824

European-Finnish (FIN) AF: 0.131 AC: 1378 AN: 10492

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13748 AN: 67920

Other (OTH) AF: 0.234 AC: 491 AN: 2100

Alfa AF: 0.240 Hom.: 623

Bravo AF: 0.255

Asia WGS AF: 0.114 AC: 397 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.52
DANN	Benign	0.13
PhyloP100		-1.7
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: rs58886660; hg19: chr2-201999283;