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.

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	Effect	Exon Rank	Protein	UniProt
CFLAR	NM_003879.7	MANE Select	c.524-370G>A	intron	N/A	NP_003870.4
CFLAR	NM_001127183.4		c.524-370G>A	intron	N/A	NP_001120655.1	O15519-1
CFLAR	NM_001308042.3		c.524-370G>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.524-370G>A	intron	N/A	ENSP00000312455.2	O15519-1
CFLAR	ENST00000423241.6	TSL:1	c.524-370G>A	intron	N/A	ENSP00000399420.2	O15519-1
CFLAR	ENST00000457277.5	TSL:1	c.524-370G>A	intron	N/A	ENSP00000411535.1	O15519-11

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over