chr2-201150305-G-T

Position:

• chr2-201150305-G-T

Variant summary

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

The NM_003879.7(CFLAR):​c.793+470G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 150,912 control chromosomes in the GnomAD database, including 5,025 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 (5021 hom., cov: 29)
  • Exomes 𝑓: 0.15 (4 hom.)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.901

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFLAR	NM_003879.7	c.793+470G>T		intron_variant		ENST00000309955.8
CFLAR-AS1	NR_040030.1	n.564-545C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFLAR	ENST00000309955.8	c.793+470G>T		intron_variant		1	NM_003879.7	P2
CFLAR-AS1	ENST00000415011.6	n.595-545C>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36139 AN: 150332 Hom.: 5002 Cov.: 29

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.0392

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.149 AC: 69 AN: 464 Hom.: 4 Cov.: 0 AF XY: 0.148 AC XY: 51 AN XY: 344

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.214

GnomAD4 genome AF: 0.241 AC: 36205 AN: 150448 Hom.: 5021 Cov.: 29 AF XY: 0.236 AC XY: 17291 AN XY: 73418

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.0395

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.231

Alfa AF: 0.131 Hom.: 235

Bravo AF: 0.248

Asia WGS AF: 0.120 AC: 421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.91
DANN	Benign	0.27

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: rs7571899; hg19: chr2-202015028;