dbSNP rs6759216: CFLAR:c.524-370G>A (chr2-201139987-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_003879.7(CFLAR):c.524-370G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 274,786 control chromosomes in the GnomAD database, including 5,101 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 0.20 ( 3641 hom., cov: 32)

Exomes 𝑓: 0.14 ( 1460 hom. )

Consequence

CFLAR
NM_003879.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.273

Publications

4 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:

IMPDH1P10 (HGNC:33965): (inosine monophosphate dehydrogenase 1 pseudogene 10)

IMPDH1P10 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_noAF=-0.68).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFLAR	NM_003879.7 link	c.524-370G>A		intron_variant	Intron 4 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.524-370G>A		intron_variant	Intron 4 of 9	1	NM_003879.7	ENSP00000312455.2		O15519-1

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30259

AN:

151824

Hom.:

3633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.162

Gnomad AMR

AF:

0.149

Gnomad ASJ

AF:

0.180

Gnomad EAS

AF:

0.0355

Gnomad SAS

AF:

0.0567

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.165

Gnomad OTH

AF:

0.189

GnomAD4 exome

AF:

0.138

AC:

17005

AN:

122846

Hom.:

1460

Cov.:

AF XY:

0.135

AC XY:

10595

AN XY:

78768

show subpopulations

African (AFR)

AF:

0.352

AC:

535

AN:

1522

American (AMR)

AF:

0.109

AC:

616

AN:

5638

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

685

AN:

4022

East Asian (EAS)

AF:

0.0147

AC:

AN:

1294

South Asian (SAS)

AF:

0.0672

AC:

1935

AN:

28782

European-Finnish (FIN)

AF:

0.140

AC:

1200

AN:

8562

Middle Eastern (MID)

AF:

0.139

AC:

AN:

440

European-Non Finnish (NFE)

AF:

0.165

AC:

11138

AN:

67360

Other (OTH)

AF:

0.156

AC:

816

AN:

5226

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

624

1247

1871

2494

3118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.199

AC:

30298

AN:

151940

Hom.:

3641

Cov.:

AF XY:

0.196

AC XY:

14529

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.331

AC:

13731

AN:

41468

American (AMR)

AF:

0.149

AC:

2274

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.180

AC:

623

AN:

3466

East Asian (EAS)

AF:

0.0358

AC:

185

AN:

5166

South Asian (SAS)

AF:

0.0565

AC:

272

AN:

4814

European-Finnish (FIN)

AF:

0.136

AC:

1433

AN:

10502

Middle Eastern (MID)

AF:

0.103

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.165

AC:

11210

AN:

67938

Other (OTH)

AF:

0.187

AC:

393

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1150

2301

3451

4602

5752

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

304

608

912

1216

1520

<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:

0.195

Hom.:

408

Bravo

AF:

0.207

Asia WGS

AF:

0.0670

AC:

234

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

9.1

(source)

DANN

Benign

0.82

PhyloP100

0.27

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over