rs1981726

Variant names:

• chr2-201143977-T-A
• rs1981726
• NM_003879.7:c.607-1401T>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.607-1401T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,100 control chromosomes in the GnomAD database, including 5,209 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 0.24 (5209 hom., cov: 32)
• Consequence: CFLAR NM_003879.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455
• 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]

CFLAR-AS1 (HGNC:14437): (CFLAR antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFLAR	NM_003879.7	c.607-1401T>A		intron_variant	Intron 5 of 9	ENST00000309955.8	NP_003870.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFLAR	ENST00000309955.8	c.607-1401T>A		intron_variant	Intron 5 of 9	1	NM_003879.7	ENSP00000312455.2

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36957 AN: 151982 Hom.: 5190 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.0397

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.243 AC: 37026 AN: 152100 Hom.: 5209 Cov.: 32 AF XY: 0.239 AC XY: 17762 AN XY: 74372

African (AFR) AF: 0.385 AC: 15986 AN: 41474

American (AMR) AF: 0.174 AC: 2664 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 967 AN: 3472

East Asian (EAS) AF: 0.0400 AC: 207 AN: 5178

South Asian (SAS) AF: 0.118 AC: 571 AN: 4824

European-Finnish (FIN) AF: 0.162 AC: 1711 AN: 10564

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14219 AN: 67986

Other (OTH) AF: 0.233 AC: 491 AN: 2110

Alfa AF: 0.242 Hom.: 603

Bravo AF: 0.248

Asia WGS AF: 0.122 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.37
DANN	Benign	0.44
PhyloP100		-0.46
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: rs1981726; hg19: chr2-202008700;