rs2271751

Variant names:

• chr10-103415374-T-C
• rs2271751
• NM_014976.2:c.1518+223T>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.1518+223T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,158 control chromosomes in the GnomAD database, including 6,682 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 0.27 (6682 hom., cov: 32)
• Consequence: PDCD11 NM_014976.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 19 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDCD11	NM_014976.2	c.1518+223T>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.1518+223T>C		intron_variant	Intron 12 of 35	1	NM_014976.2	ENSP00000358812.3
PDCD11	ENST00000649849.1	c.1518+223T>C		intron_variant	Intron 12 of 35			ENSP00000498205.1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41288 AN: 152040 Hom.: 6678 Cov.: 32

Gnomad AFR AF: 0.0929

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.271 AC: 41293 AN: 152158 Hom.: 6682 Cov.: 32 AF XY: 0.278 AC XY: 20696 AN XY: 74374

African (AFR) AF: 0.0926 AC: 3848 AN: 41542

American (AMR) AF: 0.300 AC: 4591 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1075 AN: 3470

East Asian (EAS) AF: 0.348 AC: 1801 AN: 5168

South Asian (SAS) AF: 0.505 AC: 2440 AN: 4832

European-Finnish (FIN) AF: 0.400 AC: 4225 AN: 10552

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22422 AN: 67992

Other (OTH) AF: 0.282 AC: 594 AN: 2110

Alfa AF: 0.290 Hom.: 2804

Bravo AF: 0.252

Asia WGS AF: 0.400 AC: 1386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.33
DANN	Benign	0.61
PhyloP100		-1.5
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: rs2271751; hg19: chr10-105175131;