chr3-187220496-CT-C

Variant names:

• chr3-187220496-CT-C
• rs376566294
• NM_001879.6:c.1910-236delA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_001879.6(MASP1):​c.1910-236delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00517 in 127,720 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0052 (0 hom., cov: 22)
• Consequence: MASP1 NM_001879.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.667
• Publications: 0 publications found

Genes affected

MASP1 (HGNC:6901): (MBL associated serine protease 1) This gene encodes a serine protease that functions as a component of the lectin pathway of complement activation. The complement pathway plays an essential role in the innate and adaptive immune response. The encoded protein is synthesized as a zymogen and is activated when it complexes with the pathogen recognition molecules of lectin pathway, the mannose-binding lectin and the ficolins. This protein is not directly involved in complement activation but may play a role as an amplifier of complement activation by cleaving complement C2 or by activating another complement serine protease, MASP-2. The encoded protein is also able to cleave fibrinogen and factor XIII and may may be involved in coagulation. A splice variant of this gene which lacks the serine protease domain functions as an inhibitor of the complement pathway. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Apr 2010]

MASP1 Gene-Disease associations (from GenCC):

• 3MC syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
• 3MC syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00517 (660/127720) while in subpopulation NFE AF = 0.00627 (391/62372). AF 95% confidence interval is 0.00576. There are 0 homozygotes in GnomAd4. There are 309 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001879.6. 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
	MASP1	NM_001879.6	MANE Plus Clinical	c.1910-236delA		intron	N/A	NP_001870.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASP1	ENST00000337774.10	TSL:1 MANE Plus Clinical	c.1910-236delA		intron	N/A	ENSP00000336792.5	P48740-1

Frequencies

GnomAD3 genomes AF: 0.00516 AC: 659 AN: 127734 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00450

Gnomad AMI AF: 0.00118

Gnomad AMR AF: 0.00158

Gnomad ASJ AF: 0.000311

Gnomad EAS AF: 0.000700

Gnomad SAS AF: 0.00332

Gnomad FIN AF: 0.0111

Gnomad MID AF: 0.00775

Gnomad NFE AF: 0.00627

Gnomad OTH AF: 0.00635

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

GnomAD4 genome AF: 0.00517 AC: 660 AN: 127720 Hom.: 0 Cov.: 22 AF XY: 0.00508 AC XY: 309 AN XY: 60788

African (AFR) AF: 0.00452 AC: 148 AN: 32722

American (AMR) AF: 0.00158 AC: 19 AN: 12024

Ashkenazi Jewish (ASJ) AF: 0.000311 AC: 1 AN: 3214

East Asian (EAS) AF: 0.000703 AC: 3 AN: 4268

South Asian (SAS) AF: 0.00334 AC: 13 AN: 3894

European-Finnish (FIN) AF: 0.0111 AC: 71 AN: 6402

Middle Eastern (MID) AF: 0.00840 AC: 2 AN: 238

European-Non Finnish (NFE) AF: 0.00627 AC: 391 AN: 62372

Other (OTH) AF: 0.00632 AC: 11 AN: 1740

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism

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: rs376566294; hg19: chr3-186938284;