NM_014976.2:c.1519-69T>C

Variant names:

• chr10-103416422-T-C
• rs7894407
• NM_014976.2:c.1519-69T>C

Variant summary

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

The NM_014976.2(PDCD11):​c.1519-69T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 1,554,042 control chromosomes in the GnomAD database, including 96,533 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 0.31 (7541 hom., cov: 32)
  • Exomes 𝑓: 0.35 (88992 hom.)
• Consequence: PDCD11 NM_014976.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02
• Publications: 24 publications found

Genes affected

PDCD11 (HGNC:13408): (programmed cell death 11) PDCD11 is a NF-kappa-B (NFKB1; 164011)-binding protein that colocalizes with U3 RNA (MIM 180710) in the nucleolus and is required for rRNA maturation and generation of 18S rRNA (Sweet et al., 2003 [PubMed 14624448]; Sweet et al., 2008 [PubMed 17654514]).[supplied by OMIM, Oct 2008]

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 (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDCD11	NM_014976.2	c.1519-69T>C		intron_variant	Intron 12 of 35	ENST00000369797.8	NP_055791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDCD11	ENST00000369797.8	c.1519-69T>C		intron_variant	Intron 12 of 35	1	NM_014976.2	ENSP00000358812.3
PDCD11	ENST00000649849.1	c.1519-69T>C		intron_variant	Intron 12 of 35			ENSP00000498205.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46857 AN: 151856 Hom.: 7530 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.322

GnomAD4 exome AF: 0.353 AC: 494948 AN: 1402068 Hom.: 88992 AF XY: 0.350 AC XY: 242861 AN XY: 693560

African (AFR) AF: 0.206 AC: 6652 AN: 32286

American (AMR) AF: 0.447 AC: 18884 AN: 42204

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 8152 AN: 23516

East Asian (EAS) AF: 0.457 AC: 17896 AN: 39166

South Asian (SAS) AF: 0.287 AC: 22766 AN: 79300

European-Finnish (FIN) AF: 0.326 AC: 16899 AN: 51772

Middle Eastern (MID) AF: 0.317 AC: 1756 AN: 5540

European-Non Finnish (NFE) AF: 0.357 AC: 381979 AN: 1070230

Other (OTH) AF: 0.344 AC: 19964 AN: 58054

GnomAD4 genome AF: 0.309 AC: 46897 AN: 151974 Hom.: 7541 Cov.: 32 AF XY: 0.309 AC XY: 22960 AN XY: 74296

African (AFR) AF: 0.210 AC: 8694 AN: 41462

American (AMR) AF: 0.379 AC: 5789 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1207 AN: 3466

East Asian (EAS) AF: 0.433 AC: 2233 AN: 5160

South Asian (SAS) AF: 0.287 AC: 1380 AN: 4810

European-Finnish (FIN) AF: 0.311 AC: 3289 AN: 10582

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23251 AN: 67918

Other (OTH) AF: 0.322 AC: 677 AN: 2100

Alfa AF: 0.324 Hom.: 1994

Bravo AF: 0.313

Asia WGS AF: 0.370 AC: 1290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.33
PhyloP100		-2.0
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: rs7894407; hg19: chr10-105176179; COSMIC: COSV63933063;