rs2525720

Positions:

• chr7-120964976-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019071.3(ING3):​c.364+138A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 621,624 control chromosomes in the GnomAD database, including 18,334 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (7123 hom., cov: 32)
  • Exomes 𝑓: 0.20 (11211 hom.)
• Consequence: ING3 NM_019071.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780

Genes affected

ING3 (HGNC:14587): (inhibitor of growth family member 3) The protein encoded by this gene is similar to ING1, a tumor suppressor protein that can interact with TP53, inhibit cell growth, and induce apoptosis. This protein contains a PHD-finger, which is a common motif in proteins involved in chromatin remodeling. This gene can activate p53 trans-activated promoters, including promoters of p21/waf1 and bax. Overexpression of this gene has been shown to inhibit cell growth and induce apoptosis. Allelic loss and reduced expression of this gene were detected in head and neck cancers. Two alternatively spliced transcript variants encoding different isoforms have been observed. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ING3	NM_019071.3	c.364+138A>G		intron_variant		ENST00000315870.10	NP_061944.2
ING3	XM_047420535.1	c.268-1650A>G		intron_variant			XP_047276491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ING3	ENST00000315870.10	c.364+138A>G		intron_variant		1	NM_019071.3	ENSP00000320566.5
ING3	ENST00000427726.5	n.268-1650A>G		intron_variant		1		ENSP00000410406.1
ING3	ENST00000431467.1	c.319+138A>G		intron_variant		2		ENSP00000388506.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42019 AN: 151924 Hom.: 7102 Cov.: 32

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.0649

Gnomad SAS AF: 0.0991

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.235

GnomAD4 exome AF: 0.201 AC: 94505 AN: 469582 Hom.: 11211 AF XY: 0.195 AC XY: 48224 AN XY: 247846

Gnomad4 AFR exome AF: 0.464

Gnomad4 AMR exome AF: 0.144

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.0505

Gnomad4 SAS exome AF: 0.0990

Gnomad4 FIN exome AF: 0.296

Gnomad4 NFE exome AF: 0.215

Gnomad4 OTH exome AF: 0.214

GnomAD4 genome AF: 0.277 AC: 42078 AN: 152042 Hom.: 7123 Cov.: 32 AF XY: 0.274 AC XY: 20341 AN XY: 74350

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.0647

Gnomad4 SAS AF: 0.0980

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.241

Alfa AF: 0.266 Hom.: 794

Bravo AF: 0.274

Asia WGS AF: 0.153 AC: 533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.82

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: rs2525720; hg19: chr7-120605030;