rs7421861

Variant names:

• chr2-241853198-A-G
• rs7421861
• NM_005018.3:c.77-218T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-241853198-A-G
• chr2-241853198-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005018.3(PDCD1):​c.77-218T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,194 control chromosomes in the GnomAD database, including 7,906 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.32 (7906 hom., cov: 34)
• Consequence: PDCD1 NM_005018.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.556
• Publications: 54 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 2-241853198-A-G is Benign according to our data. Variant chr2-241853198-A-G is described in ClinVar as Benign. ClinVar VariationId is 1286750.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDCD1	NM_005018.3	c.77-218T>C		intron_variant	Intron 1 of 4	ENST00000334409.10	NP_005009.2
LOC105373977	XR_924076.2	n.219A>G		non_coding_transcript_exon_variant	Exon 1 of 2
PDCD1	XM_006712573.3	c.77-218T>C		intron_variant	Intron 1 of 3		XP_006712636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDCD1	ENST00000334409.10	c.77-218T>C		intron_variant	Intron 1 of 4	1	NM_005018.3	ENSP00000335062.5

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48235 AN: 152076 Hom.: 7902 Cov.: 34

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.317 AC: 48282 AN: 152194 Hom.: 7906 Cov.: 34 AF XY: 0.320 AC XY: 23780 AN XY: 74416

African (AFR) AF: 0.254 AC: 10524 AN: 41510

American (AMR) AF: 0.287 AC: 4384 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1035 AN: 3470

East Asian (EAS) AF: 0.156 AC: 810 AN: 5176

South Asian (SAS) AF: 0.370 AC: 1785 AN: 4828

European-Finnish (FIN) AF: 0.415 AC: 4406 AN: 10616

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24244 AN: 67982

Other (OTH) AF: 0.306 AC: 647 AN: 2114

Alfa AF: 0.328 Hom.: 19705

Bravo AF: 0.301

Asia WGS AF: 0.277 AC: 962 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	-0.94
CADD	Benign	1.0
DANN	Benign	0.26
PhyloP100		-0.56
PromoterAI		0.052	Neutral
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: rs7421861; hg19: chr2-242795350;