rs777539793

Variant names:

• chr4-183445061-C-G
• rs777539793
• NM_017632.4:c.264C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-183445061-C-G
• chr4-183445061-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_017632.4(CDKN2AIP):​c.264C>G​(p.Leu88Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,430,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L88L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CDKN2AIP NM_017632.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640
• Publications: 1 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=-0.64 with no splicing effect.

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.264C>G	p.Leu88Leu	synonymous	Exon 1 of 3	NP_060102.1	Q9NXV6
	CDKN2AIP	NM_001317343.2		c.264C>G	p.Leu88Leu	synonymous	Exon 1 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.264C>G	p.Leu88Leu	synonymous	Exon 1 of 3	ENSP00000427108.1	Q9NXV6
	CDKN2AIP	ENST00000855690.1		c.264C>G	p.Leu88Leu	synonymous	Exon 1 of 3	ENSP00000525749.1
	CDKN2AIP	ENST00000510928.1	TSL:2	c.264C>G	p.Leu88Leu	synonymous	Exon 1 of 2	ENSP00000421308.1	D6RGD2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000415 AC: 1 AN: 240870 AF XY: 0.00000766

Gnomad AFR exome AF: 0.0000635

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1430450 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 705112

African (AFR) AF: 0.0000306 AC: 1 AN: 32630

American (AMR) AF: 0.00 AC: 0 AN: 43486

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25460

East Asian (EAS) AF: 0.00 AC: 0 AN: 38668

South Asian (SAS) AF: 0.00 AC: 0 AN: 84754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5658

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1088668

Other (OTH) AF: 0.00 AC: 0 AN: 58836

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	7.6
DANN	Benign	0.80
PhyloP100		-0.64
PromoterAI		-0.029	Neutral

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

dbSNP: rs777539793; hg19: chr4-184366214;