10-110874160-T-C

Variant names:

• chr10-110874160-T-C
• rs11195360
• NM_014456.5:c.-62-1806T>C

Variant summary

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

The NM_014456.5(PDCD4):​c.-62-1806T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 152,058 control chromosomes in the GnomAD database, including 26,107 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 (26107 hom., cov: 32)
• Consequence: PDCD4 NM_014456.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.681
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDCD4	NM_014456.5	c.-62-1806T>C		intron_variant	Intron 1 of 11	ENST00000280154.12	NP_055271.2
PDCD4	NM_145341.4	c.-179-1806T>C		intron_variant	Intron 1 of 12		NP_663314.1
PDCD4	NM_001199492.2	c.-62-1806T>C		intron_variant	Intron 1 of 11		NP_001186421.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDCD4	ENST00000280154.12	c.-62-1806T>C		intron_variant	Intron 1 of 11	1	NM_014456.5	ENSP00000280154.7

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84540 AN: 151940 Hom.: 26116 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.556 AC: 84541 AN: 152058 Hom.: 26107 Cov.: 32 AF XY: 0.554 AC XY: 41191 AN XY: 74326

African (AFR) AF: 0.297 AC: 12302 AN: 41458

American (AMR) AF: 0.589 AC: 9010 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 2398 AN: 3470

East Asian (EAS) AF: 0.326 AC: 1690 AN: 5182

South Asian (SAS) AF: 0.418 AC: 2017 AN: 4824

European-Finnish (FIN) AF: 0.739 AC: 7812 AN: 10574

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47314 AN: 67942

Other (OTH) AF: 0.569 AC: 1202 AN: 2112

Alfa AF: 0.647 Hom.: 123910

Bravo AF: 0.540

Asia WGS AF: 0.364 AC: 1268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.3
DANN	Benign	0.79
PhyloP100		0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs11195360; hg19: chr10-112633918;