rs10787287

Variant names:

• chr10-110887437-C-T
• rs10787287
• NM_014456.5:c.556-228C>T

Variant summary

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

The NM_014456.5(PDCD4):​c.556-228C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 152,066 control chromosomes in the GnomAD database, including 43,202 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 0.75 (43202 hom., cov: 32)
• Consequence: PDCD4 NM_014456.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDCD4	NM_014456.5	c.556-228C>T		intron_variant	Intron 5 of 11	ENST00000280154.12	NP_055271.2
PDCD4	NM_145341.4	c.523-228C>T		intron_variant	Intron 6 of 12		NP_663314.1
PDCD4	NM_001199492.2	c.514-228C>T		intron_variant	Intron 5 of 11		NP_001186421.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDCD4	ENST00000280154.12	c.556-228C>T		intron_variant	Intron 5 of 11	1	NM_014456.5	ENSP00000280154.7

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114046 AN: 151948 Hom.: 43189 Cov.: 32

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.752

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

GnomAD4 genome AF: 0.750 AC: 114097 AN: 152066 Hom.: 43202 Cov.: 32 AF XY: 0.752 AC XY: 55891 AN XY: 74340

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.844

Gnomad4 ASJ AF: 0.768

Gnomad4 EAS AF: 0.871

Gnomad4 SAS AF: 0.718

Gnomad4 FIN AF: 0.792

Gnomad4 NFE AF: 0.775

Gnomad4 OTH AF: 0.743

Alfa AF: 0.776 Hom.: 62577

Bravo AF: 0.752

Asia WGS AF: 0.752 AC: 2612 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.3
DANN	Benign	0.68

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: rs10787287; hg19: chr10-112647195;