chr12-108623874-GGAGTGGTCTGTGCCTCCGTGGGCACTGGTT-G

Position:

• chr12-108623874-GGAGTGGTCTGTGCCTCCGTGGGCACTGGTT-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BA1

The NM_003006.4(SELPLG):​c.404_433del​(p.Gln135_Thr144del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,611,826 control chromosomes in the GnomAD database, including 30,506 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2345 hom., cov: 28)
  • Exomes 𝑓: 0.19 (28161 hom.)
• Consequence: SELPLG NM_003006.4 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.03

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_003006.4.
• BP6: Variant 12-108623874-GGAGTGGTCTGTGCCTCCGTGGGCACTGGTT-G is Benign according to our data. Variant chr12-108623874-GGAGTGGTCTGTGCCTCCGTGGGCACTGGTT-G is described in ClinVar as [Benign]. Clinvar id is 768578.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SELPLG	NM_003006.4	c.404_433del	p.Gln135_Thr144del	inframe_deletion	2/2	ENST00000550948.2	NP_002997.2
SELPLG	NM_001206609.2	c.452_481del	p.Gln151_Thr160del	inframe_deletion	2/2		NP_001193538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELPLG	ENST00000550948.2	c.404_433del	p.Gln135_Thr144del	inframe_deletion	2/2	1	NM_003006.4	ENSP00000447752	P2
SELPLG	ENST00000228463.6	c.452_481del	p.Gln151_Thr160del	inframe_deletion	2/2	2		ENSP00000228463	A2
SELPLG	ENST00000388962.4	c.390+14_403del		splice_acceptor_variant, coding_sequence_variant, intron_variant	2/2	5		ENSP00000373614	A2

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25018 AN: 150428 Hom.: 2332 Cov.: 28

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0940

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.107

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.156

GnomAD3 exomes AF: 0.176 AC: 44070 AN: 249806 Hom.: 4074 AF XY: 0.182 AC XY: 24520 AN XY: 134992

Gnomad AFR exome AF: 0.111

Gnomad AMR exome AF: 0.104

Gnomad ASJ exome AF: 0.0871

Gnomad EAS exome AF: 0.359

Gnomad SAS exome AF: 0.225

Gnomad FIN exome AF: 0.183

Gnomad NFE exome AF: 0.173

Gnomad OTH exome AF: 0.164

GnomAD4 exome AF: 0.190 AC: 278052 AN: 1461282 Hom.: 28161 AF XY: 0.192 AC XY: 139512 AN XY: 726964

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.0916

Gnomad4 EAS exome AF: 0.399

Gnomad4 SAS exome AF: 0.229

Gnomad4 FIN exome AF: 0.191

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.190

GnomAD4 genome AF: 0.167 AC: 25068 AN: 150544 Hom.: 2345 Cov.: 28 AF XY: 0.168 AC XY: 12386 AN XY: 73520

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.0940

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.159

Alfa AF: 0.158 Hom.: 296

Asia WGS AF: 0.246 AC: 854 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 22, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs63748999; hg19: chr12-109017650;