2-201167704-A-G

Position:

• chr2-201167704-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003879.7(CFLAR):​c.*3731A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,910 control chromosomes in the GnomAD database, including 17,411 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 0.48 (17406 hom., cov: 31)
  • Exomes 𝑓: 0.64 (5 hom.)
• Consequence: CFLAR NM_003879.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.551

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFLAR	NM_003879.7	c.*3731A>G		3_prime_UTR_variant	10/10	ENST00000309955.8	NP_003870.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFLAR	ENST00000309955.8	c.*3731A>G		3_prime_UTR_variant	10/10	1	NM_003879.7	ENSP00000312455	P2

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72109 AN: 151770 Hom.: 17385 Cov.: 31

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.467

GnomAD4 exome AF: 0.636 AC: 14 AN: 22 Hom.: 5 Cov.: 0 AF XY: 0.667 AC XY: 12 AN XY: 18

Gnomad4 AMR exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.714

GnomAD4 genome AF: 0.475 AC: 72172 AN: 151888 Hom.: 17406 Cov.: 31 AF XY: 0.468 AC XY: 34761 AN XY: 74222

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.473

Alfa AF: 0.500 Hom.: 11174

Bravo AF: 0.468

Asia WGS AF: 0.318 AC: 1108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.30

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

Publications

LitVar

Other links and lift over

dbSNP: rs10200857; hg19: chr2-202032427;