chr4-183446316-C-T

Variant names:

• chr4-183446316-C-T
• NM_017632.4:c.632C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017632.4(CDKN2AIP):​c.632C>T​(p.Ser211Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDKN2AIP NM_017632.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.842
• Publications: 0 publications found

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]

ACMG classification

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=0.051707476).

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.632C>T	p.Ser211Phe	missense	Exon 3 of 3	NP_060102.1	Q9NXV6
	CDKN2AIP	NM_001317343.2		c.*220C>T		3_prime_UTR	Exon 3 of 3	NP_001304272.1	J3KNE1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2AIP	ENST00000504169.2	TSL:1 MANE Select	c.632C>T	p.Ser211Phe	missense	Exon 3 of 3	ENSP00000427108.1	Q9NXV6
	CDKN2AIP	ENST00000855690.1		c.629C>T	p.Ser210Phe	missense	Exon 3 of 3	ENSP00000525749.1
	CDKN2AIP	ENST00000302350.4	TSL:2	c.*220C>T		3_prime_UTR	Exon 3 of 3	ENSP00000303788.4	J3KNE1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Benign	0.17
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.84
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.042
Sift	Benign	0.69	T
Sift4G	Uncertain	0.046	D
Polyphen		0.0	B
Vest4		0.16
MutPred		0.42		Gain of catalytic residue at S211 (P = 0.0022)
MVP		0.043
MPC		0.064
ClinPred		0.024	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.048
gMVP		0.35
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

hg19: chr4-184367469;