Variant 2-241858748-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005018.3(PDCD1):c.76+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0398 in 1,576,328 control chromosomes in the GnomAD database, including 7,994 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.058 ( 1050 hom., cov: 33)

Exomes 𝑓: 0.038 ( 6944 hom. )

Consequence

PDCD1
NM_005018.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0530

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 2-241858748-G-A is Benign according to our data. Variant chr2-241858748-G-A is described in ClinVar as [Benign]. Clinvar id is 1177788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDCD1	NM_005018.3 linkuse as main transcript	c.76+15C>T		intron_variant		ENST00000334409.10
PDCD1	XM_006712573.3 linkuse as main transcript	c.76+15C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDCD1	ENST00000334409.10 linkuse as main transcript	c.76+15C>T		intron_variant		1	NM_005018.3	P1
PDCD1	ENST00000418831.1 linkuse as main transcript	c.76+15C>T		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0581

AC:

8804

AN:

151558

Hom.:

1044

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0405

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.490

Gnomad SAS

AF:

0.0777

Gnomad FIN

AF:

0.0534

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0117

Gnomad OTH

AF:

0.0654

GnomAD3 exomes

AF:

0.0988

AC:

19199

AN:

194390

Hom.:

3126

AF XY:

0.0893

AC XY:

9316

AN XY:

104312

show subpopulations

Gnomad AFR exome

AF:

0.0458

Gnomad AMR exome

AF:

0.260

Gnomad ASJ exome

AF:

0.0131

Gnomad EAS exome

AF:

0.499

Gnomad SAS exome

AF:

0.0625

Gnomad FIN exome

AF:

0.0519

Gnomad NFE exome

AF:

0.0120

Gnomad OTH exome

AF:

0.0661

GnomAD4 exome

AF:

0.0378

AC:

53881

AN:

1424662

Hom.:

6944

Cov.:

AF XY:

0.0375

AC XY:

26450

AN XY:

705530

show subpopulations

Gnomad4 AFR exome

AF:

0.0432

Gnomad4 AMR exome

AF:

0.256

Gnomad4 ASJ exome

AF:

0.0136

Gnomad4 EAS exome

AF:

0.501

Gnomad4 SAS exome

AF:

0.0635

Gnomad4 FIN exome

AF:

0.0503

Gnomad4 NFE exome

AF:

0.0113

Gnomad4 OTH exome

AF:

0.0498

GnomAD4 genome

AF:

0.0583

AC:

8839

AN:

151666

Hom.:

1050

Cov.:

AF XY:

0.0667

AC XY:

4949

AN XY:

74152

show subpopulations

Gnomad4 AFR

AF:

0.0408

Gnomad4 AMR

AF:

0.179

Gnomad4 ASJ

AF:

0.0112

Gnomad4 EAS

AF:

0.489

Gnomad4 SAS

AF:

0.0780

Gnomad4 FIN

AF:

0.0534

Gnomad4 NFE

AF:

0.0117

Gnomad4 OTH

AF:

0.0680

Alfa

AF:

0.0305

Hom.:

Bravo

AF:

0.0717

Asia WGS

AF:

0.257

AC:

894

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 38% of patients studied by a panel of primary immunodeficiencies. Number of patients: 36. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

Cadd

Benign

8.0

Dann

Benign

0.92

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