ENST00000395148.6:c.*3040G>C

Variant names:

• chr2-201139467-G-C
• rs10184098
• ENST00000395148.6:c.*3040G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000395148.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFLAR	NM_003879.7	MANE Select	c.524-890G>C		intron	N/A	NP_003870.4
	CFLAR	NM_001308043.2		c.*3040G>C		3_prime_UTR	Exon 5 of 5	NP_001294972.1	E9PAP3
	CFLAR	NM_001127183.4		c.524-890G>C		intron	N/A	NP_001120655.1	O15519-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFLAR	ENST00000395148.6	TSL:1	c.*3040G>C		3_prime_UTR	Exon 5 of 5	ENSP00000378580.2	E9PAP3
	CFLAR	ENST00000309955.8	TSL:1 MANE Select	c.524-890G>C		intron	N/A	ENSP00000312455.2	O15519-1
	CFLAR	ENST00000423241.6	TSL:1	c.524-890G>C		intron	N/A	ENSP00000399420.2	O15519-1

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

African (AFR) AF: 0.571 AC: 8 AN: 14

American (AMR) AF: 0.120 AC: 34 AN: 284

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 5 AN: 18

East Asian (EAS) AF: 0.00 AC: 0 AN: 54

South Asian (SAS) AF: 0.109 AC: 20 AN: 184

European-Finnish (FIN) AF: 0.125 AC: 3 AN: 24

Middle Eastern (MID) AF: 0.125 AC: 1 AN: 8

European-Non Finnish (NFE) AF: 0.162 AC: 272 AN: 1684

Other (OTH) AF: 0.155 AC: 17 AN: 110

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

African (AFR) AF: 0.598 AC: 24731 AN: 41326

American (AMR) AF: 0.199 AC: 3027 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 972 AN: 3470

East Asian (EAS) AF: 0.0406 AC: 210 AN: 5168

South Asian (SAS) AF: 0.120 AC: 576 AN: 4798

European-Finnish (FIN) AF: 0.164 AC: 1722 AN: 10518

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14412 AN: 67736

Other (OTH) AF: 0.277 AC: 578 AN: 2090

Alfa AF: 0.125 Hom.: 190

Bravo AF: 0.319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.86
DANN	Benign	0.35
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10184098;

hg19: chr2-202004190;