rs6476985

Positions:

• chr9-5517559-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PDCD1LG2	NM_025239.4	c.-14-4974C>T		intron_variant		ENST00000397747.5
LOC124902114	XR_007061406.1	n.255+6977G>A		intron_variant, non_coding_transcript_variant
PDCD1LG2	XM_005251600.4	c.-14-4974C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDCD1LG2	ENST00000397747.5	c.-14-4974C>T		intron_variant		1	NM_025239.4	P1
	ENST00000661858.1	n.276+6977G>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.224

Alfa AF: 0.160 Hom.: 2139

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

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

Other links and lift over

dbSNP: rs6476985; hg19: chr9-5517559;