1-11047382-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 30 publications found

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]

MASP2 Gene-Disease associations (from GenCC):

• immunodeficiency due to MASP-2 deficiency

  Inheritance: AR Classification: STRONG Submitted by: Laboratory for Molecular Medicine

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 (NFE) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006610.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASP2	NM_006610.4	MANE Select	c.-175C>A		upstream_gene	N/A	NP_006601.2
	MASP2	NM_139208.3		c.-175C>A		upstream_gene	N/A	NP_631947.1	O00187-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASP2	ENST00000400897.8	TSL:1 MANE Select	c.-175C>A		upstream_gene	N/A	ENSP00000383690.3	O00187-1
	MASP2	ENST00000400898.3	TSL:1	c.-175C>A		upstream_gene	N/A	ENSP00000383691.3	O00187-2
	MASP2	ENST00000480221.1	TSL:1	n.-155C>A		upstream_gene	N/A

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

African (AFR) AF: 0.224 AC: 3444 AN: 15362

American (AMR) AF: 0.714 AC: 13081 AN: 18324

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 8530 AN: 14376

East Asian (EAS) AF: 0.746 AC: 23366 AN: 31306

South Asian (SAS) AF: 0.647 AC: 30259 AN: 46760

European-Finnish (FIN) AF: 0.760 AC: 22473 AN: 29568

Middle Eastern (MID) AF: 0.691 AC: 1495 AN: 2162

European-Non Finnish (NFE) AF: 0.788 AC: 308758 AN: 391606

Other (OTH) AF: 0.707 AC: 21389 AN: 30272

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

African (AFR) AF: 0.247 AC: 10265 AN: 41488

American (AMR) AF: 0.684 AC: 10451 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2102 AN: 3470

East Asian (EAS) AF: 0.733 AC: 3767 AN: 5142

South Asian (SAS) AF: 0.641 AC: 3089 AN: 4816

European-Finnish (FIN) AF: 0.752 AC: 7945 AN: 10568

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.785 AC: 53330 AN: 67948

Other (OTH) AF: 0.656 AC: 1386 AN: 2114

Alfa AF: 0.732 Hom.: 70962

Bravo AF: 0.595

Asia WGS AF: 0.650 AC: 2260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.15
DANN	Benign	0.58
PhyloP100		-0.61
PromoterAI		-0.0084	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs7548659; hg19: chr1-11107439;