rs34819629

Variant names:

• chr2-241852468-C-A
• rs34819629
• NM_005018.3:c.437-115G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-241852468-C-A
• chr2-241852468-C-G
• chr2-241852468-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005018.3(PDCD1):​c.437-115G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDCD1 NM_005018.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98
• Publications: 2 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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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.437-115G>T		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.437-115G>T		intron	N/A	ENSP00000335062.5
	PDCD1	ENST00000343705.4	TSL:1	c.436+153G>T		intron	N/A	ENSP00000340808.4
	PDCD1	ENST00000418831.1	TSL:1	n.201-115G>T		intron	N/A	ENSP00000390296.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 997562 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 497770

African (AFR) AF: 0.00 AC: 0 AN: 23038

American (AMR) AF: 0.00 AC: 0 AN: 22868

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17666

East Asian (EAS) AF: 0.00 AC: 0 AN: 34324

South Asian (SAS) AF: 0.00 AC: 0 AN: 59664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41644

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3078

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 751280

Other (OTH) AF: 0.00 AC: 0 AN: 44000

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.69
PhyloP100		-2.0
PromoterAI		0.0034	Neutral

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: rs34819629; hg19: chr2-242794620;