Variant chr2-201160763-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003879.7(CFLAR):c.1125G>A(p.Val375Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,614,100 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 8 hom., cov: 31)

Exomes 𝑓: 0.0020 ( 67 hom. )

Consequence

CFLAR
NM_003879.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.317

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:

CFLAR (HGNC:):

CFLAR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 2-201160763-G-A is Benign according to our data. Variant chr2-201160763-G-A is described in ClinVar as [Benign]. Clinvar id is 773850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.317 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00201 (2934/1461840) while in subpopulation AMR AF= 0.0395 (1766/44718). AF 95% confidence interval is 0.038. There are 67 homozygotes in gnomad4_exome. There are 1257 alleles in male gnomad4_exome subpopulation. Median coverage is 35. This position pass quality control queck.

BS2

High AC in GnomAd4 at 322 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFLAR	NM_003879.7 linkuse as main transcript	c.1125G>A	p.Val375Val	synonymous_variant	9/10	ENST00000309955.8	NP_003870.4	O15519-1A0A024R3Y4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFLAR	ENST00000309955.8 linkuse as main transcript	c.1125G>A	p.Val375Val	synonymous_variant	9/10	1	NM_003879.7	ENSP00000312455.2		O15519-1

Frequencies

GnomAD3 genomes

AF:

0.00212

AC:

322

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0135

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00923

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00723

AC:

1817

AN:

251352

Hom.:

AF XY:

0.00534

AC XY:

725

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.000678

Gnomad AMR exome

AF:

0.0440

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00892

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000748

Gnomad OTH exome

AF:

0.00505

GnomAD4 exome

AF:

0.00201

AC:

2934

AN:

1461840

Hom.:

Cov.:

AF XY:

0.00173

AC XY:

1257

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.0395

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0187

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000294

Gnomad4 OTH exome

AF:

0.00129

GnomAD4 genome

AF:

0.00211

AC:

322

AN:

152260

Hom.:

Cov.:

AF XY:

0.00210

AC XY:

156

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000963

Gnomad4 AMR

AF:

0.0135

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00925

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000956

Hom.:

Bravo

AF:

0.00403

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

2.9

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over