2-201139467-G-C

Variant summary

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

The ENST00000395148.6(CFLAR):c.*3040G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,540 control chromosomes in the GnomAD database, including 9,718 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 0.31 (9718 hom., cov: 31)
  • Exomes 𝑓: 0.15 (32 hom.)
  • Failed GnomAD Quality Control
• Consequence: CFLAR ENST00000395148.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFLAR	NM_003879.7	c.524-890G>C		intron_variant		ENST00000309955.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFLAR	ENST00000309955.8	c.524-890G>C		intron_variant		1	NM_003879.7	P2
IMPDH1P10	ENST00000440965.1	n.55-464C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46362 AN: 151422 Hom.: 9691 Cov.: 31

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.0403

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.271

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.151 AC: 360 AN: 2380 Hom.: 32 Cov.: 0 AF XY: 0.160 AC XY: 231 AN XY: 1446

Gnomad4 AFR exome AF: 0.571

Gnomad4 AMR exome AF: 0.120

Gnomad4 ASJ exome AF: 0.278

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.162

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.307 AC: 46451 AN: 151540 Hom.: 9718 Cov.: 31 AF XY: 0.300 AC XY: 22211 AN XY: 74056

Gnomad4 AFR AF: 0.598

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.0406

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.277

Alfa AF: 0.125 Hom.: 190

Bravo AF: 0.319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.86
Dann	Benign	0.35

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: rs10184098; hg19: chr2-202004190;