1-11044313-C-T

Variant names:

• chr1-11044313-C-T
• rs3765900
• NM_006610.4:c.545-778G>A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MASP2	NM_006610.4	c.545-778G>A		intron_variant	Intron 4 of 10	ENST00000400897.8	NP_006601.2
MASP2	XM_017000097.1	c.545-778G>A		intron_variant	Intron 4 of 6		XP_016855586.1
MASP2	XM_047439758.1	c.544+1095G>A		intron_variant	Intron 4 of 4		XP_047295714.1
MASP2	XR_001736931.1	n.577-778G>A		intron_variant	Intron 4 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MASP2	ENST00000400897.8	c.545-778G>A		intron_variant	Intron 4 of 10	1	NM_006610.4	ENSP00000383690.3

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

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.737

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.762

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.775

Gnomad4 NFE AF: 0.782

Gnomad4 OTH AF: 0.744

Alfa AF: 0.761 Hom.: 10436

Bravo AF: 0.734

Asia WGS AF: 0.697 AC: 2425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.14
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs3765900; hg19: chr1-11104370;