rs13424615

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003879.7(CFLAR):c.607C>A(p.Leu203Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00392 in 1,597,212 control chromosomes in the GnomAD database, including 223 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 114 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 109 hom. )

Consequence

CFLAR
NM_003879.7 missense, splice_region

Scores

Splicing: ADA: 0.00005668

Clinical Significance

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

Conservation

PhyloP100: -0.264

Publications

6 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:

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

CFLAR-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014910996).

BP6

Variant 2-201145378-C-A is Benign according to our data. Variant chr2-201145378-C-A is described in ClinVar as Benign. ClinVar VariationId is 783347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0685 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003879.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CFLAR	NM_003879.7	MANE Select	c.607C>A	p.Leu203Ile	missense splice_region	Exon 6 of 10	NP_003870.4
CFLAR	NM_001127183.4		c.607C>A	p.Leu203Ile	missense splice_region	Exon 6 of 10	NP_001120655.1	O15519-1
CFLAR	NM_001308042.3		c.607C>A	p.Leu203Ile	missense splice_region	Exon 6 of 10	NP_001294971.1	O15519-11

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CFLAR	ENST00000309955.8	TSL:1 MANE Select	c.607C>A	p.Leu203Ile	missense splice_region	Exon 6 of 10	ENSP00000312455.2	O15519-1
CFLAR	ENST00000423241.6	TSL:1	c.607C>A	p.Leu203Ile	missense splice_region	Exon 6 of 10	ENSP00000399420.2	O15519-1
CFLAR	ENST00000457277.5	TSL:1	c.607C>A	p.Leu203Ile	missense splice_region	Exon 5 of 9	ENSP00000411535.1	O15519-11

Frequencies

GnomAD3 genomes

AF:

0.0205

AC:

3120

AN:

152140

Hom.:

114

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0708

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00708

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.0191

GnomAD2 exomes

AF:

0.00529

AC:

1325

AN:

250390

AF XY:

0.00400

show subpopulations

Gnomad AFR exome

AF:

0.0701

Gnomad AMR exome

AF:

0.00283

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000423

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00217

AC:

3131

AN:

1444954

Hom.:

109

Cov.:

AF XY:

0.00191

AC XY:

1377

AN XY:

719786

show subpopulations

African (AFR)

AF:

0.0728

AC:

2397

AN:

32904

American (AMR)

AF:

0.00360

AC:

160

AN:

44488

Ashkenazi Jewish (ASJ)

AF:

0.00134

AC:

AN:

26030

East Asian (EAS)

AF:

0.00

AC:

AN:

39584

South Asian (SAS)

AF:

0.000176

AC:

AN:

85440

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.0101

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.000186

AC:

204

AN:

1097520

Other (OTH)

AF:

0.00438

AC:

262

AN:

59844

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

120

240

360

480

600

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0205

AC:

3123

AN:

152258

Hom.:

114

Cov.:

AF XY:

0.0191

AC XY:

1420

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0706

AC:

2935

AN:

41544

American (AMR)

AF:

0.00707

AC:

108

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000827

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000412

AC:

AN:

68016

Other (OTH)

AF:

0.0189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

144

289

433

578

722

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00811

Hom.:

Bravo

AF:

0.0226

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0688

AC:

303

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00647

AC:

786

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000771

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.075

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0015

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

PhyloP100

-0.26

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.20

REVEL

Benign

0.072

Sift

Benign

0.14

Sift4G

Benign

0.10

Polyphen

0.18

Vest4

0.20

MVP

0.51

MPC

0.34

ClinPred

0.022

GERP RS

1.6

Varity_R

0.12

gMVP

0.32

Mutation Taster

=79/21

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000057

dbscSNV1_RF

Benign

0.0080

SpliceAI score (max)

0.030

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over