dbSNP rs10190751: CFLAR:c.606+934G>A (chr2-201141373-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001127184.4(CFLAR):c.607-1G>A variant causes a splice acceptor, 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. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.25 ( 5673 hom., cov: 32)

Exomes 𝑓: 0.20 ( 29180 hom. )

Consequence

CFLAR
NM_001127184.4 splice_acceptor, intron

Scores

Splicing: ADA: 0.00001420

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.209

Publications

43 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127184.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CFLAR	NM_003879.7	MANE Select	c.606+934G>A	intron	N/A	NP_003870.4
CFLAR	NM_001127183.4		c.606+934G>A	intron	N/A	NP_001120655.1	O15519-1
CFLAR	NM_001308042.3		c.606+934G>A	intron	N/A	NP_001294971.1	O15519-11

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CFLAR	ENST00000309955.8	TSL:1 MANE Select	c.606+934G>A	intron	N/A	ENSP00000312455.2	O15519-1
CFLAR	ENST00000423241.6	TSL:1	c.606+934G>A	intron	N/A	ENSP00000399420.2	O15519-1
CFLAR	ENST00000457277.5	TSL:1	c.606+934G>A	intron	N/A	ENSP00000411535.1	O15519-11

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

GnomAD2 exomes

AF:

0.176

AC:

28696

AN:

163388

AF XY:

0.172

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 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

African (AFR)

AF:

0.424

AC:

13548

AN:

31970

American (AMR)

AF:

0.130

AC:

4675

AN:

35866

Ashkenazi Jewish (ASJ)

AF:

0.262

AC:

6601

AN:

25206

East Asian (EAS)

AF:

0.0206

AC:

767

AN:

37254

South Asian (SAS)

AF:

0.132

AC:

10519

AN:

79588

European-Finnish (FIN)

AF:

0.161

AC:

7971

AN:

49382

Middle Eastern (MID)

AF:

0.201

AC:

1143

AN:

5690

European-Non Finnish (NFE)

AF:

0.202

AC:

218606

AN:

1080444

Other (OTH)

AF:

0.202

AC:

11743

AN:

58176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

10630

21259

31889

42518

53148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7626

15252

22878

30504

38130

<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:

0.252

AC:

38241

AN:

151990

Hom.:

5673

Cov.:

AF XY:

0.247

AC XY:

18330

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.414

AC:

17162

AN:

41444

American (AMR)

AF:

0.177

AC:

2697

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.280

AC:

971

AN:

3472

East Asian (EAS)

AF:

0.0406

AC:

210

AN:

5172

South Asian (SAS)

AF:

0.119

AC:

574

AN:

4818

European-Finnish (FIN)

AF:

0.161

AC:

1692

AN:

10528

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.209

AC:

14218

AN:

67964

Other (OTH)

AF:

0.239

AC:

504

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1371

2742

4114

5485

6856

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<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:

0.219

Hom.:

16023

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.94

BayesDel_noAF

Benign

-0.97

CADD

Benign

7.8

(source)

DANN

Benign

0.24

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00053

PhyloP100

-0.21

GERP RS

-4.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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