chr12-6652690-C-G

Variant names:

• chr12-6652690-C-G
• rs764644678
• NM_016162.4:c.469G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016162.4(ING4):​c.469G>C​(p.Ala157Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,613,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: ING4 NM_016162.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40
• Publications: 1 publications found

Genes affected

ING4 (HGNC:19423): (inhibitor of growth family member 4) This gene encodes a tumor suppressor protein that contains a PHD-finger, which is a common motif in proteins involved in chromatin remodeling. This protein can bind TP53 and EP300/p300, a component of the histone acetyl transferase complex, suggesting its involvement in the TP53-dependent regulatory pathway. Multiple alternatively spliced transcript variants have been observed that encode distinct proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14678872).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016162.4. 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
	ING4	NM_016162.4	MANE Select	c.469G>C	p.Ala157Pro	missense	Exon 5 of 8	NP_057246.2
	ING4	NM_001127582.2		c.472G>C	p.Ala158Pro	missense	Exon 5 of 8	NP_001121054.1	Q9UNL4-1
	ING4	NM_001127583.2		c.463G>C	p.Ala155Pro	missense	Exon 5 of 8	NP_001121055.1	Q9UNL4-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ING4	ENST00000341550.9	TSL:1 MANE Select	c.469G>C	p.Ala157Pro	missense	Exon 5 of 8	ENSP00000343396.4	Q9UNL4-2
	ING4	ENST00000396807.8	TSL:1	c.472G>C	p.Ala158Pro	missense	Exon 5 of 8	ENSP00000380024.4	Q9UNL4-1
	ING4	ENST00000412586.6	TSL:1	c.463G>C	p.Ala155Pro	missense	Exon 5 of 8	ENSP00000412705.2	Q9UNL4-5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152180 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000557 AC: 14 AN: 251458 AF XY: 0.0000515

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000703

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000239 AC: 35 AN: 1461782 Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20 AN XY: 727186

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000497 AC: 13 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111990

Other (OTH) AF: 0.0000662 AC: 4 AN: 60384

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152180 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74360

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000203 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

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	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.77	N
PhyloP100		2.4
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.044
Sift	Benign	0.35	T
Sift4G	Benign	0.32	T
Polyphen		0.16	B
Vest4		0.48
MutPred		0.32		Gain of glycosylation at A158 (P = 0.0173)
MVP		0.75
MPC		0.98
ClinPred		0.084	T
GERP RS		2.8
Varity_R		0.096
gMVP		0.61
Mutation Taster		=62/38	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

dbSNP: rs764644678; hg19: chr12-6761856;