rs10200857

Variant names:

• chr2-201167704-A-G
• rs10200857
• NM_003879.7:c.*3731A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003879.7(CFLAR):​c.*3731A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,910 control chromosomes in the GnomAD database, including 17,411 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 0.48 (17406 hom., cov: 31)
  • Exomes 𝑓: 0.64 (5 hom.)
• Consequence: CFLAR NM_003879.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.551
• 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]

ENSG00000234431 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003879.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFLAR	NM_003879.7	MANE Select	c.*3731A>G		3_prime_UTR	Exon 10 of 10	NP_003870.4
	CFLAR	NR_147242.2		n.2524A>G		non_coding_transcript_exon	Exon 12 of 12
	CFLAR	NR_147243.2		n.3086A>G		non_coding_transcript_exon	Exon 11 of 11

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFLAR	ENST00000309955.8	TSL:1 MANE Select	c.*3731A>G		3_prime_UTR	Exon 10 of 10	ENSP00000312455.2
	ENSG00000234431	ENST00000434645.1	TSL:5	n.*158A>G		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72109 AN: 151770 Hom.: 17385 Cov.: 31

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.467

GnomAD4 exome AF: 0.636 AC: 14 AN: 22 Hom.: 5 Cov.: 0 AF XY: 0.667 AC XY: 12 AN XY: 18

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 3 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.714 AC: 10 AN: 14

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.475 AC: 72172 AN: 151888 Hom.: 17406 Cov.: 31 AF XY: 0.468 AC XY: 34761 AN XY: 74222

African (AFR) AF: 0.473 AC: 19584 AN: 41396

American (AMR) AF: 0.411 AC: 6271 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1807 AN: 3470

East Asian (EAS) AF: 0.246 AC: 1272 AN: 5174

South Asian (SAS) AF: 0.353 AC: 1700 AN: 4818

European-Finnish (FIN) AF: 0.492 AC: 5185 AN: 10532

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34851 AN: 67924

Other (OTH) AF: 0.473 AC: 999 AN: 2110

Alfa AF: 0.501 Hom.: 15992

Bravo AF: 0.468

Asia WGS AF: 0.318 AC: 1108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.30
PhyloP100		-0.55
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

Other links and lift over

dbSNP: rs10200857; hg19: chr2-202032427;