chr12-108631651-C-T

Variant names:

• chr12-108631651-C-T
• rs8179116
• NM_003006.4:c.-6+2089G>A

Variant summary

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

The NM_003006.4(SELPLG):​c.-6+2089G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 in 152,106 control chromosomes in the GnomAD database, including 124 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 0.021 (124 hom., cov: 32)
• Consequence: SELPLG NM_003006.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• Publications: 12 publications found

Genes affected

SELPLG (HGNC:10722): (selectin P ligand) This gene encodes a glycoprotein that functions as a high affinity counter-receptor for the cell adhesion molecules P-, E- and L- selectin expressed on myeloid cells and stimulated T lymphocytes. As such, this protein plays a critical role in leukocyte trafficking during inflammation by tethering of leukocytes to activated platelets or endothelia expressing selectins. This protein requires two post-translational modifications, tyrosine sulfation and the addition of the sialyl Lewis x tetrasaccharide (sLex) to its O-linked glycans, for its high-affinity binding activity. Aberrant expression of this gene and polymorphisms in this gene are associated with defects in the innate and adaptive immune response. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Apr 2011]

ENSG00000257221 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELPLG	NM_003006.4	c.-6+2089G>A		intron_variant	Intron 1 of 1	ENST00000550948.2	NP_002997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELPLG	ENST00000550948.2	c.-6+2089G>A		intron_variant	Intron 1 of 1	1	NM_003006.4	ENSP00000447752.1

Frequencies

GnomAD3 genomes AF: 0.0209 AC: 3171 AN: 151988 Hom.: 123 Cov.: 32

Gnomad AFR AF: 0.0722

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00970

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0134

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

GnomAD4 genome AF: 0.0209 AC: 3181 AN: 152106 Hom.: 124 Cov.: 32 AF XY: 0.0201 AC XY: 1491 AN XY: 74362

African (AFR) AF: 0.0722 AC: 2995 AN: 41470

American (AMR) AF: 0.00969 AC: 148 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 67978

Other (OTH) AF: 0.0133 AC: 28 AN: 2108

Alfa AF: 0.0116 Hom.: 172

Bravo AF: 0.0243

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.18
PhyloP100		-2.2
PromoterAI		-0.016	Neutral
Mutation Taster		=100/0	polymorphism

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: rs8179116; hg19: chr12-109025427;