dbSNP rs41386349: PDCD1:c.627+252C>T (chr2-241851697-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005018.3(PDCD1):c.627+252C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 149,066 control chromosomes in the GnomAD database, including 904 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.10 ( 904 hom., cov: 32)

Consequence

PDCD1
NM_005018.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.50

Publications

31 publications found

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 Gene-Disease associations (from GenCC):

systemic lupus erythematosus
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

PDCD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 2-241851697-G-A is Benign according to our data. Variant chr2-241851697-G-A is described in ClinVar as Benign. ClinVar VariationId is 1270664.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDCD1	NM_005018.3 link	c.627+252C>T		intron_variant	Intron 4 of 4	ENST00000334409.10	NP_005009.2	Q15116A0A0M3M0G7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDCD1	ENST00000334409.10 link	c.627+252C>T		intron_variant	Intron 4 of 4	1	NM_005018.3	ENSP00000335062.5		Q15116

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15351

AN:

148962

Hom.:

911

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.103

Gnomad EAS

AF:

0.219

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.0572

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.0831

Gnomad OTH

AF:

0.119

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

GnomAD4 genome

AF:

0.103

AC:

15347

AN:

149066

Hom.:

904

Cov.:

AF XY:

0.103

AC XY:

7483

AN XY:

72762

show subpopulations

African (AFR)

AF:

0.112

AC:

4418

AN:

39364

American (AMR)

AF:

0.150

AC:

2272

AN:

15152

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

356

AN:

3464

East Asian (EAS)

AF:

0.218

AC:

1110

AN:

5092

South Asian (SAS)

AF:

0.126

AC:

595

AN:

4716

European-Finnish (FIN)

AF:

0.0572

AC:

597

AN:

10442

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0831

AC:

5616

AN:

67574

Other (OTH)

AF:

0.118

AC:

244

AN:

2066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

670

1339

2009

2678

3348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

178

356

534

712

890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0942

Hom.:

Bravo

AF:

0.116

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

1.3

(source)

DANN

Benign

0.77

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over