chr2-201129817-C-T

Variant names:

• chr2-201129817-C-T
• rs10931931
• NM_003879.7:c.-49C>T

Variant summary

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

The NM_003879.7(CFLAR):​c.-49C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,573,690 control chromosomes in the GnomAD database, including 18,773 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 0.19 (3747 hom., cov: 31)
  • Exomes 𝑓: 0.14 (15026 hom.)
• Consequence: CFLAR NM_003879.7 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.766
• Publications: 15 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFLAR	NM_003879.7	c.-49C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 10	ENST00000309955.8	NP_003870.4
CFLAR	NM_003879.7	c.-49C>T		5_prime_UTR_variant	Exon 2 of 10	ENST00000309955.8	NP_003870.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFLAR	ENST00000309955.8	c.-49C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 10	1	NM_003879.7	ENSP00000312455.2
CFLAR	ENST00000309955.8	c.-49C>T		5_prime_UTR_variant	Exon 2 of 10	1	NM_003879.7	ENSP00000312455.2

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29309 AN: 151912 Hom.: 3741 Cov.: 31

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.00732

Gnomad SAS AF: 0.0441

Gnomad FIN AF: 0.0922

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.178

GnomAD2 exomes AF: 0.127 AC: 29885 AN: 234756 AF XY: 0.123

Gnomad AFR exome AF: 0.373

Gnomad AMR exome AF: 0.0956

Gnomad ASJ exome AF: 0.149

Gnomad EAS exome AF: 0.00461

Gnomad FIN exome AF: 0.0985

Gnomad NFE exome AF: 0.145

Gnomad OTH exome AF: 0.140

GnomAD4 exome AF: 0.137 AC: 194504 AN: 1421660 Hom.: 15026 Cov.: 27 AF XY: 0.134 AC XY: 94515 AN XY: 704718

African (AFR) AF: 0.362 AC: 11818 AN: 32646

American (AMR) AF: 0.103 AC: 4408 AN: 42772

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 3703 AN: 24098

East Asian (EAS) AF: 0.00247 AC: 97 AN: 39288

South Asian (SAS) AF: 0.0520 AC: 4284 AN: 82362

European-Finnish (FIN) AF: 0.0977 AC: 5104 AN: 52232

Middle Eastern (MID) AF: 0.139 AC: 778 AN: 5614

European-Non Finnish (NFE) AF: 0.144 AC: 156126 AN: 1083922

Other (OTH) AF: 0.139 AC: 8186 AN: 58726

GnomAD4 genome AF: 0.193 AC: 29347 AN: 152030 Hom.: 3747 Cov.: 31 AF XY: 0.187 AC XY: 13886 AN XY: 74326

African (AFR) AF: 0.356 AC: 14757 AN: 41410

American (AMR) AF: 0.149 AC: 2271 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 564 AN: 3472

East Asian (EAS) AF: 0.00734 AC: 38 AN: 5180

South Asian (SAS) AF: 0.0439 AC: 212 AN: 4828

European-Finnish (FIN) AF: 0.0922 AC: 975 AN: 10574

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 10007 AN: 67964

Other (OTH) AF: 0.176 AC: 371 AN: 2110

Alfa AF: 0.176 Hom.: 845

Bravo AF: 0.206

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.3
DANN	Benign	0.45
PhyloP100		-0.77
PromoterAI		-0.044	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
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: rs10931931; hg19: chr2-201994540;