rs6476985

Variant names:

• chr9-5517559-C-T
• rs6476985
• NM_025239.4:c.-14-4974C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025239.4(PDCD1LG2):​c.-14-4974C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,136 control chromosomes in the GnomAD database, including 8,856 homozygotes. 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: 𝑓 0.27 (8856 hom., cov: 32)
• Consequence: PDCD1LG2 NM_025239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.787
• Publications: 7 publications found

Genes affected

PDCD1LG2 (HGNC:18731): (programmed cell death 1 ligand 2) Involved in negative regulation of activated T cell proliferation; negative regulation of interferon-gamma production; and negative regulation of interleukin-10 production. Predicted to be located in plasma membrane. Predicted to be active in external side of plasma membrane. Biomarker of pulmonary tuberculosis. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286162 (HGNC:56906):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDCD1LG2	NM_025239.4	c.-14-4974C>T		intron_variant	Intron 1 of 6	ENST00000397747.5	NP_079515.2
PDCD1LG2	XM_005251600.4	c.-14-4974C>T		intron_variant	Intron 1 of 6		XP_005251657.1
INCR1	XR_007061406.1	n.255+6977G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDCD1LG2	ENST00000397747.5	c.-14-4974C>T		intron_variant	Intron 1 of 6	1	NM_025239.4	ENSP00000380855.3
ENSG00000286162	ENST00000661858.1	n.276+6977G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41451 AN: 152018 Hom.: 8817 Cov.: 32

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.273 AC: 41541 AN: 152136 Hom.: 8856 Cov.: 32 AF XY: 0.272 AC XY: 20248 AN XY: 74380

African (AFR) AF: 0.582 AC: 24141 AN: 41476

American (AMR) AF: 0.223 AC: 3413 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 473 AN: 3472

East Asian (EAS) AF: 0.465 AC: 2398 AN: 5154

South Asian (SAS) AF: 0.180 AC: 867 AN: 4830

European-Finnish (FIN) AF: 0.143 AC: 1515 AN: 10578

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8031 AN: 68014

Other (OTH) AF: 0.224 AC: 475 AN: 2116

Alfa AF: 0.174 Hom.: 8773

Bravo AF: 0.295

Asia WGS AF: 0.297 AC: 1033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.46
DANN	Benign	0.48
PhyloP100		-0.79
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: rs6476985; hg19: chr9-5517559;