1-11047382-G-T

Variant names:

• chr1-11047382-G-T
• rs7548659
• NM_006610.4:c.-175C>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006610.4(MASP2):​c.-175C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 731,760 control chromosomes in the GnomAD database, including 198,026 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 0.61 (32658 hom., cov: 31)
  • Exomes 𝑓: 0.75 (165368 hom.)
• Consequence: MASP2 NM_006610.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.608

Genes affected

MASP2 (HGNC:6902): (MBL associated serine protease 2) This gene encodes a member of the peptidase S1 family of serine proteases. The encoded preproprotein is proteolytically processed to generate A and B chains that heterodimerize to form the mature protease. This protease cleaves complement components C2 and C4 in order to generate C3 convertase in the lectin pathway of the complement system. The encoded protease also plays a role in the coagulation cascade through cleavage of prothrombin to form thrombin. Myocardial infarction and acute stroke patients exhibit reduced serum concentrations of the encoded protein. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MASP2	NM_006610.4	c.-175C>A		upstream_gene_variant		ENST00000400897.8	NP_006601.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MASP2	ENST00000400897.8	c.-175C>A		upstream_gene_variant		1	NM_006610.4	ENSP00000383690.3

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93289 AN: 151904 Hom.: 32652 Cov.: 31

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.653

GnomAD4 exome AF: 0.747 AC: 432795 AN: 579736 Hom.: 165368 AF XY: 0.743 AC XY: 219965 AN XY: 296002

Gnomad4 AFR exome AF: 0.224

Gnomad4 AMR exome AF: 0.714

Gnomad4 ASJ exome AF: 0.593

Gnomad4 EAS exome AF: 0.746

Gnomad4 SAS exome AF: 0.647

Gnomad4 FIN exome AF: 0.760

Gnomad4 NFE exome AF: 0.788

Gnomad4 OTH exome AF: 0.707

GnomAD4 genome AF: 0.614 AC: 93300 AN: 152024 Hom.: 32658 Cov.: 31 AF XY: 0.612 AC XY: 45474 AN XY: 74298

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.733

Gnomad4 SAS AF: 0.641

Gnomad4 FIN AF: 0.752

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.656

Alfa AF: 0.746 Hom.: 57957

Bravo AF: 0.595

Asia WGS AF: 0.650 AC: 2260 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	0.15
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7548659; hg19: chr1-11107439;