2-201144863-G-A

Position:

• chr2-201144863-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.607-515G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 150,498 control chromosomes in the GnomAD database, including 3,297 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 0.20 (3297 hom., cov: 32)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFLAR	NM_003879.7	c.607-515G>A		intron_variant		ENST00000309955.8	NP_003870.4
CFLAR-AS1	NR_040030.1	n.884+3871C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFLAR	ENST00000309955.8	c.607-515G>A		intron_variant		1	NM_003879.7	ENSP00000312455	P2
CFLAR-AS1	ENST00000415011.6	n.915+3871C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29474 AN: 150378 Hom.: 3295 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.0360

Gnomad SAS AF: 0.0591

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.113

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.194

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.196 AC: 29498 AN: 150498 Hom.: 3297 Cov.: 32 AF XY: 0.192 AC XY: 14121 AN XY: 73360

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.0363

Gnomad4 SAS AF: 0.0589

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.192

Alfa AF: 0.184 Hom.: 348

Bravo AF: 0.201

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.58
DANN	Benign	0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs10203550; hg19: chr2-202009586;