chr2-201147640-C-G

Variant names:

• chr2-201147640-C-G
• rs13413075
• NM_003879.7:c.662-1363C>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.662-1363C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 151,914 control chromosomes in the GnomAD database, including 5,162 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 0.24 (5159 hom., cov: 31)
  • Exomes 𝑓: 0.29 (3 hom.)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.24
• Publications: 5 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFLAR	NM_003879.7	c.662-1363C>G		intron_variant	Intron 6 of 9	ENST00000309955.8	NP_003870.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFLAR	ENST00000309955.8	c.662-1363C>G		intron_variant	Intron 6 of 9	1	NM_003879.7	ENSP00000312455.2

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36809 AN: 151722 Hom.: 5140 Cov.: 31

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.0398

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.289 AC: 22 AN: 76 Hom.: 3 AF XY: 0.250 AC XY: 14 AN XY: 56

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.273 AC: 18 AN: 66

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.243 AC: 36877 AN: 151838 Hom.: 5159 Cov.: 31 AF XY: 0.239 AC XY: 17706 AN XY: 74228

African (AFR) AF: 0.384 AC: 15893 AN: 41366

American (AMR) AF: 0.174 AC: 2657 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 967 AN: 3468

East Asian (EAS) AF: 0.0401 AC: 207 AN: 5158

South Asian (SAS) AF: 0.119 AC: 571 AN: 4812

European-Finnish (FIN) AF: 0.161 AC: 1690 AN: 10522

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14194 AN: 67946

Other (OTH) AF: 0.231 AC: 488 AN: 2110

Alfa AF: 0.242 Hom.: 604

Bravo AF: 0.248

Asia WGS AF: 0.121 AC: 423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.24
DANN	Benign	0.34
PhyloP100		-2.2
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: rs13413075; hg19: chr2-202012363;