Genetic Variant NM_013399.3:c.89G>A (chr16-4513848-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_013399.3(CDIP1):c.89G>A(p.Arg30His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000637 in 1,568,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

CDIP1
NM_013399.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.338

Publications

0 publications found

Variant links:

Genes affected

CDIP1 (HGNC:13234): (cell death inducing p53 target 1) Predicted to enable metal ion binding activity. Acts upstream of or within intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator and tumor necrosis factor-mediated signaling pathway. Located in cytoplasmic side of late endosome membrane; cytoplasmic side of lysosomal membrane; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CDIP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.050955176).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013399.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDIP1	NM_013399.3	MANE Select	c.89G>A	p.Arg30His	missense	Exon 4 of 6	NP_037531.2	Q9H305-1
CDIP1	NM_001199054.2		c.89G>A	p.Arg30His	missense	Exon 4 of 6	NP_001185983.1	Q9H305-1
CDIP1	NM_001199055.2		c.89G>A	p.Arg30His	missense	Exon 4 of 6	NP_001185984.1	Q9H305-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDIP1	ENST00000567695.6	TSL:1 MANE Select	c.89G>A	p.Arg30His	missense	Exon 4 of 6	ENSP00000457877.1	Q9H305-1
CDIP1	ENST00000399599.7	TSL:1	c.89G>A	p.Arg30His	missense	Exon 3 of 5	ENSP00000382508.2	Q9H305-1
CDIP1	ENST00000563332.6	TSL:1	c.89G>A	p.Arg30His	missense	Exon 4 of 6	ENSP00000454994.1	Q9H305-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000735

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000343

AC:

AN:

203944

AF XY:

0.0000546

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000755

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000649

AC:

AN:

1416502

Hom.:

Cov.:

AF XY:

0.0000613

AC XY:

AN XY:

701268

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32038

American (AMR)

AF:

0.0000262

AC:

AN:

38138

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22608

East Asian (EAS)

AF:

0.00

AC:

AN:

38948

South Asian (SAS)

AF:

0.0000127

AC:

AN:

78912

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51128

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5514

European-Non Finnish (NFE)

AF:

0.0000807

AC:

AN:

1090734

Other (OTH)

AF:

0.0000342

AC:

AN:

58482

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

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:

0.0000526

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41432

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68016

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.000130

Hom.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.0000662

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

0.090

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.013

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.66

M_CAP

Benign

0.037

MetaRNN

Benign

0.051

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.69

PhyloP100

0.34

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.47

REVEL

Benign

0.097

Sift

Benign

0.14

Sift4G

Benign

0.14

Polyphen

0.0

Vest4

0.13

MVP

0.35

MPC

0.24

ClinPred

0.095

GERP RS

3.5

PromoterAI

-0.050

Neutral

(source)

Varity_R

0.085

gMVP

0.20

Mutation Taster

=91/9

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