10-110878270-T-G

Variant names:

• chr10-110878270-T-G
• rs1407696
• NM_014456.5:c.43+2200T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014456.5(PDCD4):​c.43+2200T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 152,022 control chromosomes in the GnomAD database, including 26,555 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 0.56 (26555 hom., cov: 32)
• Consequence: PDCD4 NM_014456.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.710
• Publications: 9 publications found

Genes affected

PDCD4 (HGNC:8763): (programmed cell death 4) This gene is a tumor suppressor and encodes a protein that binds to the eukaryotic translation initiation factor 4A1 and inhibits its function by preventing RNA binding. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDCD4	NM_014456.5	c.43+2200T>G		intron_variant	Intron 2 of 11	ENST00000280154.12	NP_055271.2
PDCD4	NM_145341.4	c.10+1517T>G		intron_variant	Intron 3 of 12		NP_663314.1
PDCD4	NM_001199492.2	c.43+2200T>G		intron_variant	Intron 2 of 11		NP_001186421.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDCD4	ENST00000280154.12	c.43+2200T>G		intron_variant	Intron 2 of 11	1	NM_014456.5	ENSP00000280154.7

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84844 AN: 151904 Hom.: 26565 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.558 AC: 84832 AN: 152022 Hom.: 26555 Cov.: 32 AF XY: 0.556 AC XY: 41331 AN XY: 74324

African (AFR) AF: 0.283 AC: 11718 AN: 41448

American (AMR) AF: 0.599 AC: 9158 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2409 AN: 3472

East Asian (EAS) AF: 0.327 AC: 1690 AN: 5176

South Asian (SAS) AF: 0.421 AC: 2032 AN: 4828

European-Finnish (FIN) AF: 0.741 AC: 7822 AN: 10552

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.706 AC: 47998 AN: 67948

Other (OTH) AF: 0.572 AC: 1206 AN: 2110

Alfa AF: 0.664 Hom.: 57162

Bravo AF: 0.541

Asia WGS AF: 0.365 AC: 1268 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.43
PhyloP100		-0.71
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: rs1407696; hg19: chr10-112638028;