dbSNP rs6759004: CFLAR:c.524-404C>T (chr2-201139953-C-T) – 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.524-404C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 203,356 control chromosomes in the GnomAD database, including 3,421 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 0.18 ( 2925 hom., cov: 32)

Exomes 𝑓: 0.12 ( 496 hom. )

Consequence

CFLAR
NM_003879.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.145

Publications

8 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=-0.72).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFLAR	NM_003879.7 link	c.524-404C>T		intron_variant	Intron 4 of 9	ENST00000309955.8	NP_003870.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFLAR	ENST00000309955.8 link	c.524-404C>T		intron_variant	Intron 4 of 9	1	NM_003879.7	ENSP00000312455.2

Frequencies

GnomAD3 genomes

AF:

0.180

AC:

27331

AN:

151966

Hom.:

2924

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.138

Gnomad ASJ

AF:

0.166

Gnomad EAS

AF:

0.0349

Gnomad SAS

AF:

0.0455

Gnomad FIN

AF:

0.120

Gnomad MID

AF:

0.102

Gnomad NFE

AF:

0.150

Gnomad OTH

AF:

0.174

GnomAD4 exome

AF:

0.121

AC:

6213

AN:

51272

Hom.:

496

Cov.:

AF XY:

0.117

AC XY:

3999

AN XY:

34082

show subpopulations

African (AFR)

AF:

0.279

AC:

125

AN:

448

American (AMR)

AF:

0.100

AC:

AN:

958

Ashkenazi Jewish (ASJ)

AF:

0.154

AC:

153

AN:

996

East Asian (EAS)

AF:

0.00456

AC:

AN:

658

South Asian (SAS)

AF:

0.0514

AC:

690

AN:

13422

European-Finnish (FIN)

AF:

0.123

AC:

488

AN:

3974

Middle Eastern (MID)

AF:

0.178

AC:

AN:

146

European-Non Finnish (NFE)

AF:

0.152

AC:

4350

AN:

28650

Other (OTH)

AF:

0.140

AC:

282

AN:

2020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

224

448

671

895

1119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.180

AC:

27345

AN:

152084

Hom.:

2925

Cov.:

AF XY:

0.176

AC XY:

13106

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.295

AC:

12251

AN:

41464

American (AMR)

AF:

0.138

AC:

2111

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.166

AC:

575

AN:

3468

East Asian (EAS)

AF:

0.0352

AC:

182

AN:

5176

South Asian (SAS)

AF:

0.0454

AC:

219

AN:

4826

European-Finnish (FIN)

AF:

0.120

AC:

1274

AN:

10584

Middle Eastern (MID)

AF:

0.0959

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.150

AC:

10225

AN:

67970

Other (OTH)

AF:

0.172

AC:

362

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1083

2166

3249

4332

5415

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

276

552

828

1104

1380

<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:

0.171

Hom.:

379

Bravo

AF:

0.188

Asia WGS

AF:

0.0580

AC:

203

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

7.4

(source)

DANN

Benign

0.90

PhyloP100

0.14

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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