chr1-11030974-G-A

Variant names:

• chr1-11030974-G-A
• rs9430176
• NM_006610.4:c.1088-92C>T

Variant summary

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

The NM_006610.4(MASP2):​c.1088-92C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.03 in 1,342,370 control chromosomes in the GnomAD database, including 1,579 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 0.046 (330 hom., cov: 31)
  • Exomes 𝑓: 0.028 (1249 hom.)
• Consequence: MASP2 NM_006610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASP2	NM_006610.4	MANE Select	c.1088-92C>T		intron	N/A	NP_006601.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASP2	ENST00000400897.8	TSL:1 MANE Select	c.1088-92C>T		intron	N/A	ENSP00000383690.3
	MASP2	ENST00000700092.1		c.1101-126C>T		intron	N/A	ENSP00000514791.1
	MASP2	ENST00000700093.1		c.1064-92C>T		intron	N/A	ENSP00000514792.1

Frequencies

GnomAD3 genomes AF: 0.0458 AC: 6958 AN: 151870 Hom.: 332 Cov.: 31

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.0307

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0100

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0187

Gnomad OTH AF: 0.0527

GnomAD4 exome AF: 0.0280 AC: 33320 AN: 1190382 Hom.: 1249 AF XY: 0.0295 AC XY: 17467 AN XY: 592096

African (AFR) AF: 0.0721 AC: 1943 AN: 26966

American (AMR) AF: 0.0198 AC: 538 AN: 27204

Ashkenazi Jewish (ASJ) AF: 0.0409 AC: 785 AN: 19182

East Asian (EAS) AF: 0.184 AC: 6527 AN: 35384

South Asian (SAS) AF: 0.0846 AC: 5419 AN: 64068

European-Finnish (FIN) AF: 0.00980 AC: 469 AN: 47872

Middle Eastern (MID) AF: 0.0465 AC: 158 AN: 3398

European-Non Finnish (NFE) AF: 0.0169 AC: 15500 AN: 916342

Other (OTH) AF: 0.0396 AC: 1981 AN: 49966

GnomAD4 genome AF: 0.0458 AC: 6964 AN: 151988 Hom.: 330 Cov.: 31 AF XY: 0.0472 AC XY: 3506 AN XY: 74292

African (AFR) AF: 0.0801 AC: 3321 AN: 41460

American (AMR) AF: 0.0305 AC: 466 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0349 AC: 121 AN: 3470

East Asian (EAS) AF: 0.204 AC: 1047 AN: 5128

South Asian (SAS) AF: 0.101 AC: 485 AN: 4790

European-Finnish (FIN) AF: 0.0100 AC: 106 AN: 10588

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0187 AC: 1273 AN: 67968

Other (OTH) AF: 0.0531 AC: 112 AN: 2110

Alfa AF: 0.0345 Hom.: 20

Bravo AF: 0.0483

Asia WGS AF: 0.129 AC: 446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.88
DANN	Benign	0.55
PhyloP100		-0.39
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: rs9430176; hg19: chr1-11091031;