rs6710479

Variant names:

• chr2-241855866-T-C
• rs6710479
• NM_005018.3:c.77-2886A>G

Variant summary

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

The NM_005018.3(PDCD1):​c.77-2886A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 151,930 control chromosomes in the GnomAD database, including 20,622 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 0.51 (20622 hom., cov: 32)
• Consequence: PDCD1 NM_005018.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.868
• Publications: 13 publications found

Genes affected

PDCD1 (HGNC:8760): (programmed cell death 1) Programmed cell death protein 1 (PDCD1) is an immune-inhibitory receptor expressed in activated T cells; it is involved in the regulation of T-cell functions, including those of effector CD8+ T cells. In addition, this protein can also promote the differentiation of CD4+ T cells into T regulatory cells. PDCD1 is expressed in many types of tumors including melanomas, and has demonstrated to play a role in anti-tumor immunity. Moreover, this protein has been shown to be involved in safeguarding against autoimmunity, however, it can also contribute to the inhibition of effective anti-tumor and anti-microbial immunity. [provided by RefSeq, Aug 2020]

PDCD1 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

LOC105373977 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005018.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDCD1	NM_005018.3	MANE Select	c.77-2886A>G		intron	N/A	NP_005009.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDCD1	ENST00000334409.10	TSL:1 MANE Select	c.77-2886A>G		intron	N/A	ENSP00000335062.5
	PDCD1	ENST00000343705.4	TSL:1	c.77-2886A>G		intron	N/A	ENSP00000340808.4
	PDCD1	ENST00000418831.1	TSL:1	n.77-2886A>G		intron	N/A	ENSP00000390296.1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77784 AN: 151812 Hom.: 20617 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.512 AC: 77819 AN: 151930 Hom.: 20622 Cov.: 32 AF XY: 0.515 AC XY: 38274 AN XY: 74284

African (AFR) AF: 0.423 AC: 17505 AN: 41420

American (AMR) AF: 0.450 AC: 6868 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 2141 AN: 3468

East Asian (EAS) AF: 0.250 AC: 1285 AN: 5150

South Asian (SAS) AF: 0.604 AC: 2910 AN: 4816

European-Finnish (FIN) AF: 0.640 AC: 6768 AN: 10578

Middle Eastern (MID) AF: 0.630 AC: 184 AN: 292

European-Non Finnish (NFE) AF: 0.566 AC: 38420 AN: 67918

Other (OTH) AF: 0.512 AC: 1082 AN: 2112

Alfa AF: 0.535 Hom.: 3669

Bravo AF: 0.489

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.2
DANN	Benign	0.81
PhyloP100		0.87
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: rs6710479; hg19: chr2-242798018;