2-201147345-A-G

Variant names:

• chr2-201147345-A-G
• rs13387186
• NM_003879.7:c.662-1658A>G

Variant summary

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

The ENST00000309955.8(CFLAR):​c.662-1658A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 151,748 control chromosomes in the GnomAD database, including 5,733 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 (5733 hom., cov: 31)
• Consequence: CFLAR ENST00000309955.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000309955.8. 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.662-1658A>G		intron	N/A	NP_003870.4
	CFLAR	NM_001127183.4		c.662-1658A>G		intron	N/A	NP_001120655.1
	CFLAR	NM_001308042.3		c.662-1658A>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.662-1658A>G		intron	N/A	ENSP00000312455.2
	CFLAR	ENST00000423241.6	TSL:1	c.662-1658A>G		intron	N/A	ENSP00000399420.2
	CFLAR	ENST00000457277.5	TSL:1	c.662-1658A>G		intron	N/A	ENSP00000411535.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38253 AN: 151624 Hom.: 5712 Cov.: 31

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.0402

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.198

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.253 AC: 38325 AN: 151748 Hom.: 5733 Cov.: 31 AF XY: 0.248 AC XY: 18376 AN XY: 74178

African (AFR) AF: 0.417 AC: 17252 AN: 41328

American (AMR) AF: 0.177 AC: 2704 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 969 AN: 3466

East Asian (EAS) AF: 0.0405 AC: 209 AN: 5164

South Asian (SAS) AF: 0.118 AC: 567 AN: 4804

European-Finnish (FIN) AF: 0.162 AC: 1702 AN: 10538

Middle Eastern (MID) AF: 0.198 AC: 57 AN: 288

European-Non Finnish (NFE) AF: 0.209 AC: 14210 AN: 67890

Other (OTH) AF: 0.238 AC: 501 AN: 2108

Alfa AF: 0.116 Hom.: 176

Bravo AF: 0.259

Asia WGS AF: 0.126 AC: 441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.5
DANN	Benign	0.81
PhyloP100		0.24
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: rs13387186; hg19: chr2-202012068;