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GeneBe

2-201160763-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_003879.7(CFLAR):c.1125G>A(p.Val375=) 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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.317 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 322 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CFLARNM_003879.7 linkuse as main transcriptc.1125G>A p.Val375= synonymous_variant 9/10 ENST00000309955.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CFLARENST00000309955.8 linkuse as main transcriptc.1125G>A p.Val375= synonymous_variant 9/101 NM_003879.7 P2O15519-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00212
AC:
322
AN:
152142
Hom.:
8
Cov.:
31
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.:
50
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.:
67
Cov.:
35
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00211
AC:
322
AN:
152260
Hom.:
8
Cov.:
31
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.:
0
Bravo
AF:
0.00403
Asia WGS
AF:
0.00491
AC:
17
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000237

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 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.

Other links and lift over

dbSNP: rs151223777; hg19: chr2-202025486; API