Genetic Variant NM_003879.7:c.606+934G>A (chr2-201141373-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003879.7(CFLAR):c.606+934G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,555,566 control chromosomes in the GnomAD database, including 34,853 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 0.25 ( 5673 hom., cov: 32)

Exomes 𝑓: 0.20 ( 29180 hom. )

Consequence

CFLAR
NM_003879.7 intron

Scores

Splicing: ADA: 0.00001420

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.209

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

CFLAR-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_addAF=-0.935885).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFLAR	NM_003879.7 link	c.606+934G>A		intron_variant	Intron 5 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.606+934G>A		intron_variant	Intron 5 of 9	1	NM_003879.7	ENSP00000312455.2		O15519-1

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38170

AN:

151872

Hom.:

5652

Cov.:

show subpopulations

Gnomad AFR

AF:

0.414

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.280

Gnomad EAS

AF:

0.0403

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.233

GnomAD3 exomes

AF:

0.176

AC:

28696

AN:

163388

Hom.:

3080

AF XY:

0.172

AC XY:

14978

AN XY:

87010

show subpopulations

Gnomad AFR exome

AF:

0.411

Gnomad AMR exome

AF:

0.120

Gnomad ASJ exome

AF:

0.259

Gnomad EAS exome

AF:

0.0329

Gnomad SAS exome

AF:

0.127

Gnomad FIN exome

AF:

0.163

Gnomad NFE exome

AF:

0.201

Gnomad OTH exome

AF:

0.193

GnomAD4 exome

AF:

0.196

AC:

275573

AN:

1403576

Hom.:

29180

Cov.:

AF XY:

0.195

AC XY:

134825

AN XY:

692730

show subpopulations

Gnomad4 AFR exome

AF:

0.424

Gnomad4 AMR exome

AF:

0.130

Gnomad4 ASJ exome

AF:

0.262

Gnomad4 EAS exome

AF:

0.0206

Gnomad4 SAS exome

AF:

0.132

Gnomad4 FIN exome

AF:

0.161

Gnomad4 NFE exome

AF:

0.202

Gnomad4 OTH exome

AF:

0.202

GnomAD4 genome

AF:

0.252

AC:

38241

AN:

151990

Hom.:

5673

Cov.:

AF XY:

0.247

AC XY:

18330

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.414

Gnomad4 AMR

AF:

0.177

Gnomad4 ASJ

AF:

0.280

Gnomad4 EAS

AF:

0.0406

Gnomad4 SAS

AF:

0.119

Gnomad4 FIN

AF:

0.161

Gnomad4 NFE

AF:

0.209

Gnomad4 OTH

AF:

0.239

Alfa

AF:

0.217

Hom.:

6973

Bravo

AF:

0.257

TwinsUK

AF:

0.198

AC:

735

ALSPAC

AF:

0.201

AC:

773

ESP6500AA

AF:

0.392

AC:

1221

ESP6500EA

AF:

0.193

AC:

1377

ExAC

AF:

0.116

AC:

12642

Asia WGS

AF:

0.125

AC:

437

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.94

BayesDel_noAF

Benign

-0.97

CADD

Benign

7.8

DANN

Benign

0.24

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00053

GERP RS

-4.6

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000014

dbscSNV1_RF

Benign

0.0

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over