NM_006093.4:c.-218C>T

Variant names:

• chr11-57381258-G-A
• rs10400305
• NM_006093.4:c.-218C>T

Variant summary

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

The NM_006093.4(PRG3):​c.-218C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 152,362 control chromosomes in the GnomAD database, including 45,103 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 0.75 (45023 hom., cov: 32)
  • Exomes 𝑓: 0.87 (80 hom.)
• Consequence: PRG3 NM_006093.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401
• Publications: 2 publications found

Genes affected

PRG3 (HGNC:9363): (proteoglycan 3, pro eosinophil major basic protein 2) An extracellular matrix structural constituent conferring compression resistance. Involved in several processes, including granulocyte activation; histamine biosynthetic process; and regulation of gene expression. Located in collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRG3	NM_006093.4	c.-218C>T		upstream_gene_variant		ENST00000287143.2	NP_006084.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRG3	ENST00000287143.2	c.-218C>T		upstream_gene_variant		1	NM_006093.4	ENSP00000287143.2

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113721 AN: 152028 Hom.: 45010 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.905

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.902

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.780

GnomAD4 exome AF: 0.866 AC: 187 AN: 216 Hom.: 80 AF XY: 0.855 AC XY: 142 AN XY: 166

African (AFR) AF: 0.750 AC: 3 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 4 AN: 4

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 1.00 AC: 10 AN: 10

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.851 AC: 160 AN: 188

Other (OTH) AF: 1.00 AC: 8 AN: 8

GnomAD4 genome AF: 0.748 AC: 113770 AN: 152146 Hom.: 45023 Cov.: 32 AF XY: 0.757 AC XY: 56336 AN XY: 74416

African (AFR) AF: 0.462 AC: 19138 AN: 41464

American (AMR) AF: 0.853 AC: 13049 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.875 AC: 3038 AN: 3472

East Asian (EAS) AF: 0.987 AC: 5114 AN: 5182

South Asian (SAS) AF: 0.885 AC: 4269 AN: 4822

European-Finnish (FIN) AF: 0.902 AC: 9567 AN: 10604

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.836 AC: 56865 AN: 67992

Other (OTH) AF: 0.782 AC: 1649 AN: 2108

Alfa AF: 0.814 Hom.: 214858

Bravo AF: 0.734

Asia WGS AF: 0.903 AC: 3138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.57
PhyloP100		-0.40
PromoterAI		0.0050	Neutral

Splicing

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

Other links and lift over

dbSNP: rs10400305; hg19: chr11-57148731;