Genetic Variant CARD19:p.Val156Ile (chr9-93113021-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032310.5(CARD19):c.466G>A(p.Val156Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,609,382 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000094 ( 1 hom. )

Consequence

CARD19
NM_032310.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0280

Publications

1 publications found

Variant links:

Genes affected

CARD19 (HGNC:28148): (caspase recruitment domain family member 19) Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

CARD19 links:

ENSG00000223446 (HGNC:):

ENSG00000223446 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.030900717).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032310.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CARD19	NM_032310.5	MANE Select	c.466G>A	p.Val156Ile	missense	Exon 6 of 6	NP_115686.3
CARD19	NM_001318011.2		c.406G>A	p.Val136Ile	missense	Exon 5 of 5	NP_001304940.1
CARD19	NM_001318010.2		c.263G>A	p.Arg88His	missense	Exon 4 of 4	NP_001304939.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CARD19	ENST00000375464.7	TSL:1 MANE Select	c.466G>A	p.Val156Ile	missense	Exon 6 of 6	ENSP00000364613.2	Q96LW7-2
CARD19	ENST00000466409.1	TSL:1	n.*1215G>A		non_coding_transcript_exon	Exon 4 of 4	ENSP00000437237.1	Q96LW7-1
CARD19	ENST00000490488.5	TSL:1	n.508G>A		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000951

AC:

AN:

241910

AF XY:

0.0000991

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.000442

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000370

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000940

AC:

137

AN:

1457316

Hom.:

Cov.:

AF XY:

0.0000773

AC XY:

AN XY:

724420

show subpopulations

African (AFR)

AF:

0.000239

AC:

AN:

33436

American (AMR)

AF:

0.000586

AC:

AN:

44394

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25958

East Asian (EAS)

AF:

0.00

AC:

AN:

39630

South Asian (SAS)

AF:

0.0000704

AC:

AN:

85206

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52894

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.0000730

AC:

AN:

1109824

Other (OTH)

AF:

0.000266

AC:

AN:

60222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.000171

AC:

AN:

152066

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.000266

AC:

AN:

41398

American (AMR)

AF:

0.000393

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68008

Other (OTH)

AF:

0.000478

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.000136

Hom.:

Bravo

AF:

0.000249

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000825

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.92

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.78

M_CAP

Benign

0.0052

MetaRNN

Benign

0.031

MetaSVM

Benign

-1.1

PhyloP100

-0.028

PROVEAN

Benign

-0.35

REVEL

Benign

0.032

Sift

Benign

0.29

Sift4G

Benign

0.30

Polyphen

0.10

Vest4

0.078

MVP

0.040

MPC

0.049

ClinPred

0.051

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.27

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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