1-11044313-C-T

Variant names:

• chr1-11044313-C-T
• rs3765900
• NM_006610.4:c.545-778G>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.545-778G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 152,038 control chromosomes in the GnomAD database, including 41,573 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 0.74 (41573 hom., cov: 32)
• Consequence: MASP2 NM_006610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98
• Publications: 9 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.777 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.545-778G>A		intron	N/A	NP_006601.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASP2	ENST00000400897.8	TSL:1 MANE Select	c.545-778G>A		intron	N/A	ENSP00000383690.3	O00187-1
	MASP2	ENST00000860329.1		c.604+179G>A		intron	N/A	ENSP00000530388.1
	MASP2	ENST00000700092.1		c.545-778G>A		intron	N/A	ENSP00000514791.1	A0A8V8TQL2

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112044 AN: 151918 Hom.: 41542 Cov.: 32

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.742

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

GnomAD4 genome AF: 0.737 AC: 112126 AN: 152038 Hom.: 41573 Cov.: 32 AF XY: 0.733 AC XY: 54501 AN XY: 74314

African (AFR) AF: 0.668 AC: 27709 AN: 41454

American (AMR) AF: 0.737 AC: 11261 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2213 AN: 3470

East Asian (EAS) AF: 0.762 AC: 3921 AN: 5144

South Asian (SAS) AF: 0.651 AC: 3140 AN: 4822

European-Finnish (FIN) AF: 0.775 AC: 8208 AN: 10592

Middle Eastern (MID) AF: 0.716 AC: 209 AN: 292

European-Non Finnish (NFE) AF: 0.782 AC: 53157 AN: 67954

Other (OTH) AF: 0.744 AC: 1571 AN: 2112

Alfa AF: 0.757 Hom.: 11663

Bravo AF: 0.734

Asia WGS AF: 0.697 AC: 2425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.14
DANN	Benign	0.76
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs3765900; hg19: chr1-11104370;