rs6759216

Positions:

• chr2-201139987-G-A
• chr2-201139987-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.524-370G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 274,786 control chromosomes in the GnomAD database, including 5,101 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 (3641 hom., cov: 32)
  • Exomes 𝑓: 0.14 (1460 hom.)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273

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]

IMPDH1P10 (HGNC:33965): (inosine monophosphate dehydrogenase 1 pseudogene 10)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFLAR	NM_003879.7	c.524-370G>A		intron_variant		ENST00000309955.8	NP_003870.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFLAR	ENST00000309955.8	c.524-370G>A		intron_variant		1	NM_003879.7	ENSP00000312455	P2
IMPDH1P10	ENST00000440965.1	n.41C>T		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30259 AN: 151824 Hom.: 3633 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.0355

Gnomad SAS AF: 0.0567

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.189

GnomAD4 exome AF: 0.138 AC: 17005 AN: 122846 Hom.: 1460 Cov.: 0 AF XY: 0.135 AC XY: 10595 AN XY: 78768

Gnomad4 AFR exome AF: 0.352

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.170

Gnomad4 EAS exome AF: 0.0147

Gnomad4 SAS exome AF: 0.0672

Gnomad4 FIN exome AF: 0.140

Gnomad4 NFE exome AF: 0.165

Gnomad4 OTH exome AF: 0.156

GnomAD4 genome AF: 0.199 AC: 30298 AN: 151940 Hom.: 3641 Cov.: 32 AF XY: 0.196 AC XY: 14529 AN XY: 74244

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.0358

Gnomad4 SAS AF: 0.0565

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.187

Alfa AF: 0.195 Hom.: 408

Bravo AF: 0.207

Asia WGS AF: 0.0670 AC: 234 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	9.1
DANN	Benign	0.82

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: rs6759216; hg19: chr2-202004710;