dbSNP rs10204525: PDCD1:c.*889G>A (chr2-241850169-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005018.3(PDCD1):c.*889G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 232,418 control chromosomes in the GnomAD database, including 9,473 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 5361 hom., cov: 34)

Exomes 𝑓: 0.22 ( 4112 hom. )

Consequence

PDCD1
NM_005018.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.198

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 2-241850169-C-T is Benign according to our data. Variant chr2-241850169-C-T is described in ClinVar as [Benign]. Clinvar id is 1255049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDCD1	NM_005018.3 link	c.*889G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000334409.10	NP_005009.2	Q15116A0A0M3M0G7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDCD1	ENST00000334409 link	c.*889G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_005018.3	ENSP00000335062.5		Q15116

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

32931

AN:

152056

Hom.:

5353

Cov.:

show subpopulations

Gnomad AFR

AF:

0.341

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.347

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.696

Gnomad SAS

AF:

0.204

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.0989

Gnomad OTH

AF:

0.226

GnomAD4 exome

AF:

0.223

AC:

17930

AN:

80246

Hom.:

4112

Cov.:

AF XY:

0.217

AC XY:

8033

AN XY:

36950

show subpopulations

Gnomad4 AFR exome

AF:

0.342

Gnomad4 AMR exome

AF:

0.393

Gnomad4 ASJ exome

AF:

0.117

Gnomad4 EAS exome

AF:

0.754

Gnomad4 SAS exome

AF:

0.203

Gnomad4 FIN exome

AF:

0.160

Gnomad4 NFE exome

AF:

0.102

Gnomad4 OTH exome

AF:

0.187

GnomAD4 genome

AF:

0.217

AC:

32979

AN:

152172

Hom.:

5361

Cov.:

AF XY:

0.223

AC XY:

16575

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.341

Gnomad4 AMR

AF:

0.348

Gnomad4 ASJ

AF:

0.118

Gnomad4 EAS

AF:

0.695

Gnomad4 SAS

AF:

0.204

Gnomad4 FIN

AF:

0.111

Gnomad4 NFE

AF:

0.0989

Gnomad4 OTH

AF:

0.228

Alfa

AF:

0.158

Hom.:

450

Bravo

AF:

0.245

Asia WGS

AF:

0.418

AC:

1454

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 29, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30540488, 25895129) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.98

DANN

Benign

0.70

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over