rs6759004

chr2-201139953-C-T

Variant summary

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

The NM_003879.7(CFLAR):c.524-404C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 203,356 control chromosomes in the GnomAD database, including 3,421 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 0.18 (2925 hom., cov: 32)
  • Exomes 𝑓: 0.12 (496 hom.)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145

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=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFLAR	NM_003879.7	c.524-404C>T		intron_variant		ENST00000309955.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFLAR	ENST00000309955.8	c.524-404C>T		intron_variant		1	NM_003879.7	P2
IMPDH1P10	ENST00000440965.1	n.54+21G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27331 AN: 151966 Hom.: 2924 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0349

Gnomad SAS AF: 0.0455

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.121 AC: 6213 AN: 51272 Hom.: 496 Cov.: 0 AF XY: 0.117 AC XY: 3999 AN XY: 34082

Gnomad4 AFR exome AF: 0.279

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.00456

Gnomad4 SAS exome AF: 0.0514

Gnomad4 FIN exome AF: 0.123

Gnomad4 NFE exome AF: 0.152

Gnomad4 OTH exome AF: 0.140

GnomAD4 genome AF: 0.180 AC: 27345 AN: 152084 Hom.: 2925 Cov.: 32 AF XY: 0.176 AC XY: 13106 AN XY: 74364

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.0352

Gnomad4 SAS AF: 0.0454

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.172

Alfa AF: 0.171 Hom.: 379

Bravo AF: 0.188

Asia WGS AF: 0.0580 AC: 203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	7.4
Dann	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6759004; hg19: chr2-202004676;