dbSNP rs777022788: CDKN2AIP:p.Ala47Asp (chr4-183444937-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2

The NM_017632.4(CDKN2AIP):c.140C>A(p.Ala47Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A47V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CDKN2AIP
NM_017632.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.930

Publications

0 publications found

Variant links:

Genes affected

CDKN2AIP (HGNC:24325): (CDKN2A interacting protein) The protein encoded by this gene regulates the DNA damage response through several different signaling pathways. One such pathway is the p53-HDM2-p21(WAF1) pathway, which is critical to the DNA damage response. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

CDKN2AIP links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.106175035).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017632.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2AIP	NM_017632.4	MANE Select	c.140C>A	p.Ala47Asp	missense	Exon 1 of 3	NP_060102.1	Q9NXV6
	CDKN2AIP	NM_001317343.2		c.140C>A	p.Ala47Asp	missense	Exon 1 of 3	NP_001304272.1	J3KNE1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDKN2AIP	ENST00000504169.2	TSL:1 MANE Select	c.140C>A	p.Ala47Asp	missense	Exon 1 of 3	ENSP00000427108.1	Q9NXV6
CDKN2AIP	ENST00000855690.1		c.140C>A	p.Ala47Asp	missense	Exon 1 of 3	ENSP00000525749.1
CDKN2AIP	ENST00000510928.1	TSL:2	c.140C>A	p.Ala47Asp	missense	Exon 1 of 2	ENSP00000421308.1	D6RGD2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000826

AC:

AN:

242012

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1458878

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725502

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33424

American (AMR)

AF:

0.00

AC:

AN:

44610

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26082

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39648

South Asian (SAS)

AF:

0.00

AC:

AN:

86178

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52072

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1110848

Other (OTH)

AF:

0.00

AC:

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.555

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

Cov.:

ExAC

AF:

0.00000826

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0035

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.71

M_CAP

Benign

0.054

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.93

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.42

REVEL

Benign

0.059

Sift

Benign

0.14

Sift4G

Benign

0.070

Polyphen

0.57

Vest4

0.29

MutPred

0.34

Gain of relative solvent accessibility (P = 0.0479)

MVP

0.13

MPC

1.6

ClinPred

0.25

GERP RS

1.8

PromoterAI

-0.0096

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.24

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over