rs12104442

Variant names:

• chr2-201149233-T-C
• rs12104442
• NM_003879.7:c.711+181T>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.711+181T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 516,362 control chromosomes in the GnomAD database, including 12,508 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 (5174 hom., cov: 32)
  • Exomes 𝑓: 0.19 (7334 hom.)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223
• Publications: 9 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 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.711+181T>C		intron	N/A	NP_003870.4
	CFLAR	NM_001127183.4		c.711+181T>C		intron	N/A	NP_001120655.1
	CFLAR	NM_001308042.3		c.711+181T>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.711+181T>C		intron	N/A	ENSP00000312455.2
	CFLAR	ENST00000423241.6	TSL:1	c.711+181T>C		intron	N/A	ENSP00000399420.2
	CFLAR	ENST00000457277.5	TSL:1	c.711+181T>C		intron	N/A	ENSP00000411535.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36864 AN: 151986 Hom.: 5155 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.0395

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.187 AC: 68166 AN: 364258 Hom.: 7334 Cov.: 4 AF XY: 0.185 AC XY: 35831 AN XY: 193306

African (AFR) AF: 0.385 AC: 4005 AN: 10396

American (AMR) AF: 0.144 AC: 2215 AN: 15402

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 2845 AN: 10992

East Asian (EAS) AF: 0.0195 AC: 504 AN: 25814

South Asian (SAS) AF: 0.131 AC: 4884 AN: 37326

European-Finnish (FIN) AF: 0.162 AC: 3885 AN: 24016

Middle Eastern (MID) AF: 0.192 AC: 319 AN: 1662

European-Non Finnish (NFE) AF: 0.208 AC: 45272 AN: 217732

Other (OTH) AF: 0.203 AC: 4237 AN: 20918

GnomAD4 genome AF: 0.243 AC: 36931 AN: 152104 Hom.: 5174 Cov.: 32 AF XY: 0.238 AC XY: 17714 AN XY: 74356

African (AFR) AF: 0.384 AC: 15913 AN: 41452

American (AMR) AF: 0.174 AC: 2664 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 966 AN: 3468

East Asian (EAS) AF: 0.0398 AC: 206 AN: 5182

South Asian (SAS) AF: 0.118 AC: 571 AN: 4830

European-Finnish (FIN) AF: 0.161 AC: 1703 AN: 10580

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

European-Non Finnish (NFE) AF: 0.209 AC: 14208 AN: 67980

Other (OTH) AF: 0.232 AC: 490 AN: 2114

Alfa AF: 0.243 Hom.: 3926

Bravo AF: 0.248

Asia WGS AF: 0.121 AC: 423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.5
DANN	Benign	0.66
PhyloP100		0.22
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: rs12104442; hg19: chr2-202013956;