chr2-241709346-C-T

Variant names:

• chr2-241709346-C-T
• rs146454591
• NM_032329.6:c.240C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_032329.6(ING5):​c.240C>T​(p.Asp80Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,613,710 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (53 hom.)
• Consequence: ING5 NM_032329.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.54
• Publications: 1 publications found

Genes affected

ING5 (HGNC:19421): (inhibitor of growth family member 5) This gene encodes a tumor suppressor protein that inhibits cell growth and induces apoptosis. This protein contains a PHD-type zinc finger. It interacts with tumor suppressor p53 and p300, a component of the histone acetyl transferase complex, suggesting a role in transcriptional regulation. Alternative splicing and the use of multiple promoters and 3' terminal exons results in multiple transcript variants. [provided by RefSeq, Aug 2016]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 2-241709346-C-T is Benign according to our data. Variant chr2-241709346-C-T is described in ClinVar as Benign. ClinVar VariationId is 781691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.54 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.003 (457/152086) while in subpopulation AMR AF = 0.0268 (408/15252). AF 95% confidence interval is 0.0246. There are 12 homozygotes in GnomAd4. There are 247 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 457 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032329.6. 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
	ING5	NM_032329.6	MANE Select	c.240C>T	p.Asp80Asp	synonymous	Exon 3 of 8	NP_115705.2
	ING5	NM_001330161.2		c.246C>T	p.Asp82Asp	synonymous	Exon 4 of 8	NP_001317090.1	A0A1B0GW41
	ING5	NM_001330162.2		c.240C>T	p.Asp80Asp	synonymous	Exon 3 of 8	NP_001317091.1	Q8WYH8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ING5	ENST00000313552.11	TSL:1 MANE Select	c.240C>T	p.Asp80Asp	synonymous	Exon 3 of 8	ENSP00000322142.7	Q8WYH8-1
	ING5	ENST00000406941.5	TSL:1	c.240C>T	p.Asp80Asp	synonymous	Exon 3 of 8	ENSP00000385937.1	Q8WYH8-2
	ING5	ENST00000948226.1		c.240C>T	p.Asp80Asp	synonymous	Exon 3 of 10	ENSP00000618285.1

Frequencies

GnomAD3 genomes AF: 0.00299 AC: 454 AN: 151968 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0266

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.00731 AC: 1834 AN: 250980 AF XY: 0.00557

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.0517

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000705

Gnomad OTH exome AF: 0.00490

GnomAD4 exome AF: 0.00151 AC: 2210 AN: 1461624 Hom.: 53 Cov.: 31 AF XY: 0.00127 AC XY: 921 AN XY: 727122

African (AFR) AF: 0.000478 AC: 16 AN: 33444

American (AMR) AF: 0.0467 AC: 2085 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86202

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53416

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.0000621 AC: 69 AN: 1111906

Other (OTH) AF: 0.000613 AC: 37 AN: 60384

GnomAD4 genome AF: 0.00300 AC: 457 AN: 152086 Hom.: 12 Cov.: 32 AF XY: 0.00332 AC XY: 247 AN XY: 74366

African (AFR) AF: 0.00104 AC: 43 AN: 41436

American (AMR) AF: 0.0268 AC: 408 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68020

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000720 Hom.: 0

Bravo AF: 0.00462

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.47
DANN	Benign	0.79
PhyloP100		-2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs146454591; hg19: chr2-242648761; COSMIC: COSV57978359;