rs2248890

Positions:

• chr7-120957939-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.267+2315A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,030 control chromosomes in the GnomAD database, including 14,731 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 0.39 (14731 hom., cov: 32)
• Consequence: ING3 NM_019071.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ING3	NM_019071.3	c.267+2315A>G		intron_variant		ENST00000315870.10
ING3	XM_047420535.1	c.267+2315A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ING3	ENST00000315870.10	c.267+2315A>G		intron_variant		1	NM_019071.3	P1
ING3	ENST00000427726.5	c.267+2315A>G		intron_variant, NMD_transcript_variant		1
ING3	ENST00000431467.1	c.222+2315A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59768 AN: 151912 Hom.: 14672 Cov.: 32

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.343

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.394 AC: 59899 AN: 152030 Hom.: 14731 Cov.: 32 AF XY: 0.396 AC XY: 29444 AN XY: 74316

Gnomad4 AFR AF: 0.696

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.350

Alfa AF: 0.336 Hom.: 1320

Bravo AF: 0.408

Asia WGS AF: 0.385 AC: 1340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.0
DANN	Benign	0.71

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: rs2248890; hg19: chr7-120597993;