chr4-183446598-T-G

Position:

• chr4-183446598-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017632.4(CDKN2AIP):​c.914T>G​(p.Leu305Arg) 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. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDKN2AIP NM_017632.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.823

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27453446).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKN2AIP	NM_017632.4	c.914T>G	p.Leu305Arg	missense_variant	3/3	ENST00000504169.2
CDKN2AIP	NM_001317343.2	c.*502T>G		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKN2AIP	ENST00000504169.2	c.914T>G	p.Leu305Arg	missense_variant	3/3	1	NM_017632.4
CDKN2AIP	ENST00000302350.4	c.*502T>G		3_prime_UTR_variant	3/3	2		P1
CDKN2AIP	ENST00000506835.1	n.727T>G		non_coding_transcript_exon_variant	3/3	2
CDKN2AIP	ENST00000502924.1	n.207+251T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.0033
Eigen_PC	Benign	0.060
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.97	L
MutationTaster	Benign	1.0	D;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.53	N
REVEL	Uncertain	0.53
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.52	T
Polyphen		0.56	P
Vest4		0.56
MutPred		0.34		Gain of glycosylation at S307 (P = 0.0114);
MVP		0.37
MPC		0.084
ClinPred		0.36	T
GERP RS		5.2
Varity_R		0.23
gMVP		0.49

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

LitVar

Other links and lift over

dbSNP: rs193921061; hg19: chr4-184367751; COSMIC: COSV56627734; COSMIC: COSV56627734;