chr2-201154487-A-G

Variant names:

• chr2-201154487-A-G
• rs56161269
• NM_003879.7:c.793+4652A>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.793+4652A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,160 control chromosomes in the GnomAD database, including 5,413 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 (5412 hom., cov: 32)
  • Exomes 𝑓: 0.26 (1 hom.)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.391 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+4652A>G		intron	N/A	NP_003870.4
	CFLAR	NM_001127183.4		c.793+4652A>G		intron	N/A	NP_001120655.1
	CFLAR	NM_001308042.3		c.793+4652A>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.793+4652A>G		intron	N/A	ENSP00000312455.2
	CFLAR	ENST00000423241.6	TSL:1	c.793+4652A>G		intron	N/A	ENSP00000399420.2
	CFLAR	ENST00000457277.5	TSL:1	c.793+4652A>G		intron	N/A	ENSP00000411535.1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37466 AN: 151994 Hom.: 5391 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.0403

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.227

GnomAD4 exome AF: 0.261 AC: 12 AN: 46 Hom.: 1 Cov.: 0 AF XY: 0.237 AC XY: 9 AN XY: 38

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.136 AC: 3 AN: 22

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.389 AC: 7 AN: 18

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.247 AC: 37536 AN: 152114 Hom.: 5412 Cov.: 32 AF XY: 0.242 AC XY: 17993 AN XY: 74376

African (AFR) AF: 0.397 AC: 16453 AN: 41490

American (AMR) AF: 0.176 AC: 2692 AN: 15280

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

East Asian (EAS) AF: 0.0405 AC: 210 AN: 5180

South Asian (SAS) AF: 0.118 AC: 571 AN: 4822

European-Finnish (FIN) AF: 0.161 AC: 1707 AN: 10588

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

European-Non Finnish (NFE) AF: 0.209 AC: 14233 AN: 67974

Other (OTH) AF: 0.233 AC: 492 AN: 2110

Alfa AF: 0.244 Hom.: 625

Bravo AF: 0.251

Asia WGS AF: 0.124 AC: 435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	6.0
DANN	Benign	0.81
PhyloP100		-0.14
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: rs56161269; hg19: chr2-202019210;