2-201171755-G-A

Position:

• chr2-201171755-G-A

Variant summary

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

The NM_003879.7(CFLAR):​c.*7782G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 152,096 control chromosomes in the GnomAD database, including 61,651 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 0.90 (61651 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: CFLAR NM_003879.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFLAR	NM_003879.7	c.*7782G>A		3_prime_UTR_variant	10/10	ENST00000309955.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFLAR	ENST00000309955.8	c.*7782G>A		3_prime_UTR_variant	10/10	1	NM_003879.7	P2

Frequencies

GnomAD3 genomes AF: 0.899 AC: 136569 AN: 151980 Hom.: 61607 Cov.: 30

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.973

Gnomad MID AF: 0.876

Gnomad NFE AF: 0.930

Gnomad OTH AF: 0.902

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.899 AC: 136671 AN: 152096 Hom.: 61651 Cov.: 30 AF XY: 0.895 AC XY: 66557 AN XY: 74332

Gnomad4 AFR AF: 0.854

Gnomad4 AMR AF: 0.892

Gnomad4 ASJ AF: 0.959

Gnomad4 EAS AF: 0.854

Gnomad4 SAS AF: 0.710

Gnomad4 FIN AF: 0.973

Gnomad4 NFE AF: 0.930

Gnomad4 OTH AF: 0.903

Alfa AF: 0.922 Hom.: 74377

Bravo AF: 0.891

Asia WGS AF: 0.763 AC: 2657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.37

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: rs7558475; hg19: chr2-202036478;