rs2518142

Variant names:

• chr2-201160408-G-A
• rs2518142
• NM_003879.7:c.794-24G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-201160408-G-A
• chr2-201160408-G-C
• chr2-201160408-G-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.794-24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 1,602,208 control chromosomes in the GnomAD database, including 638,173 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.88 (59435 hom., cov: 30)
  • Exomes 𝑓: 0.89 (578738 hom.)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13
• Publications: 10 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: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFLAR	NM_003879.7	c.794-24G>A		intron_variant	Intron 8 of 9	ENST00000309955.8	NP_003870.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFLAR	ENST00000309955.8	c.794-24G>A		intron_variant	Intron 8 of 9	1	NM_003879.7	ENSP00000312455.2

Frequencies

GnomAD3 genomes AF: 0.882 AC: 134086 AN: 151976 Hom.: 59392 Cov.: 30

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.867

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.970

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.910

Gnomad OTH AF: 0.874

GnomAD2 exomes AF: 0.870 AC: 213615 AN: 245416 AF XY: 0.865

Gnomad AFR exome AF: 0.840

Gnomad AMR exome AF: 0.840

Gnomad ASJ exome AF: 0.934

Gnomad EAS exome AF: 0.872

Gnomad FIN exome AF: 0.964

Gnomad NFE exome AF: 0.909

Gnomad OTH exome AF: 0.886

GnomAD4 exome AF: 0.891 AC: 1292656 AN: 1450114 Hom.: 578738 Cov.: 41 AF XY: 0.886 AC XY: 638864 AN XY: 720878

African (AFR) AF: 0.831 AC: 27575 AN: 33174

American (AMR) AF: 0.845 AC: 37319 AN: 44154

Ashkenazi Jewish (ASJ) AF: 0.936 AC: 24195 AN: 25860

East Asian (EAS) AF: 0.819 AC: 32414 AN: 39592

South Asian (SAS) AF: 0.704 AC: 60433 AN: 85882

European-Finnish (FIN) AF: 0.961 AC: 46380 AN: 48252

Middle Eastern (MID) AF: 0.832 AC: 4774 AN: 5736

European-Non Finnish (NFE) AF: 0.909 AC: 1006354 AN: 1107402

Other (OTH) AF: 0.886 AC: 53212 AN: 60062

GnomAD4 genome AF: 0.882 AC: 134186 AN: 152094 Hom.: 59435 Cov.: 30 AF XY: 0.880 AC XY: 65410 AN XY: 74362

African (AFR) AF: 0.843 AC: 34935 AN: 41460

American (AMR) AF: 0.866 AC: 13233 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.933 AC: 3239 AN: 3472

East Asian (EAS) AF: 0.856 AC: 4416 AN: 5160

South Asian (SAS) AF: 0.696 AC: 3342 AN: 4800

European-Finnish (FIN) AF: 0.970 AC: 10286 AN: 10604

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.910 AC: 61908 AN: 68006

Other (OTH) AF: 0.875 AC: 1848 AN: 2112

Alfa AF: 0.896 Hom.: 172232

Bravo AF: 0.874

Asia WGS AF: 0.752 AC: 2618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.070
DANN	Benign	0.43
PhyloP100		-2.1
BranchPoint Hunter		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2518142; hg19: chr2-202025131;