rs2041765

Variant names:

• chr2-201158437-G-A
• rs2041765
• NM_003879.7:c.794-1995G>A

Variant summary

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

The NM_003879.7(CFLAR):​c.794-1995G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 152,120 control chromosomes in the GnomAD database, including 16,501 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 0.46 (16501 hom., cov: 33)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.653
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFLAR	NM_003879.7	c.794-1995G>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.794-1995G>A		intron_variant	Intron 8 of 9	1	NM_003879.7	ENSP00000312455.2

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70069 AN: 152002 Hom.: 16481 Cov.: 33

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.456

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.461 AC: 70129 AN: 152120 Hom.: 16501 Cov.: 33 AF XY: 0.455 AC XY: 33832 AN XY: 74390

African (AFR) AF: 0.421 AC: 17469 AN: 41496

American (AMR) AF: 0.409 AC: 6245 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1844 AN: 3472

East Asian (EAS) AF: 0.247 AC: 1278 AN: 5176

South Asian (SAS) AF: 0.347 AC: 1676 AN: 4828

European-Finnish (FIN) AF: 0.493 AC: 5222 AN: 10586

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34920 AN: 67972

Other (OTH) AF: 0.463 AC: 976 AN: 2110

Alfa AF: 0.491 Hom.: 12570

Bravo AF: 0.452

Asia WGS AF: 0.308 AC: 1075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	13
DANN	Benign	0.55
PhyloP100		0.65
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: rs2041765; hg19: chr2-202023160;