rs7585993

chr2-201150391-T-G

Variant summary

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

The NM_003879.7(CFLAR):c.793+556T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 150,620 control chromosomes in the GnomAD database, including 5,621 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 (5614 hom., cov: 30)
  • Exomes 𝑓: 0.19 (7 hom.)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFLAR	NM_003879.7	c.793+556T>G		intron_variant		ENST00000309955.8
CFLAR-AS1	NR_040030.1	n.564-631A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFLAR	ENST00000309955.8	c.793+556T>G		intron_variant		1	NM_003879.7	P2
CFLAR-AS1	ENST00000415011.6	n.595-631A>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 37897 AN: 150112 Hom.: 5593 Cov.: 30

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.0406

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.205

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.234

GnomAD4 exome AF: 0.188 AC: 75 AN: 398 Hom.: 7 Cov.: 0 AF XY: 0.164 AC XY: 50 AN XY: 304

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.250

Gnomad4 EAS exome AF: 0.0455

Gnomad4 SAS exome AF: 0.111

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.278

GnomAD4 genome AF: 0.253 AC: 37966 AN: 150222 Hom.: 5614 Cov.: 30 AF XY: 0.248 AC XY: 18174 AN XY: 73256

Gnomad4 AFR AF: 0.415

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.0409

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.240

Alfa AF: 0.246 Hom.: 645

Bravo AF: 0.257

Asia WGS AF: 0.125 AC: 438 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	2.3
Dann	Benign	0.42

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: rs7585993; hg19: chr2-202015114;