Genetic Variant CFLAR:c.524-370G>T (chr2-201139987-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003879.7(CFLAR):c.524-370G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CFLAR
NM_003879.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.273

Publications

4 publications found

Variant links:

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 links:

IMPDH1P10 (HGNC:33965): (inosine monophosphate dehydrogenase 1 pseudogene 10)

IMPDH1P10 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFLAR	NM_003879.7 link	c.524-370G>T		intron_variant	Intron 4 of 9	ENST00000309955.8	NP_003870.4	O15519-1A0A024R3Y4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFLAR	ENST00000309955.8 link	c.524-370G>T		intron_variant	Intron 4 of 9	1	NM_003879.7	ENSP00000312455.2		O15519-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

123070

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

78890

African (AFR)

AF:

0.00

AC:

AN:

1528

American (AMR)

AF:

0.00

AC:

AN:

5650

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4028

East Asian (EAS)

AF:

0.00

AC:

AN:

1294

South Asian (SAS)

AF:

0.00

AC:

AN:

28830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

440

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67488

Other (OTH)

AF:

0.00

AC:

AN:

5230

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

6.2

(source)

DANN

Benign

0.76

PhyloP100

0.27

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over