3-187220496-CTTTTTTTTTTTT-CTTTTTTTTTTTTTT

Variant names:

• chr3-187220496-C-CTT
• rs376566294
• NM_001879.6:c.1910-237_1910-236dupAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001879.6(MASP1):​c.1910-237_1910-236dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 127,736 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0022 (3 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00222 (284/127736) while in subpopulation EAS AF = 0.0075 (32/4266). AF 95% confidence interval is 0.00546. There are 3 homozygotes in GnomAd4. There are 123 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.1910-237_1910-236dupAA		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.1910-236_1910-235insAA		intron	N/A	ENSP00000336792.5	P48740-1

Frequencies

GnomAD3 genomes AF: 0.00222 AC: 284 AN: 127750 Hom.: 3 Cov.: 22

Gnomad AFR AF: 0.00370

Gnomad AMI AF: 0.00118

Gnomad AMR AF: 0.00233

Gnomad ASJ AF: 0.000622

Gnomad EAS AF: 0.00747

Gnomad SAS AF: 0.00280

Gnomad FIN AF: 0.000312

Gnomad MID AF: 0.00385

Gnomad NFE AF: 0.00123

Gnomad OTH AF: 0.00520

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

GnomAD4 genome AF: 0.00222 AC: 284 AN: 127736 Hom.: 3 Cov.: 22 AF XY: 0.00202 AC XY: 123 AN XY: 60800

African (AFR) AF: 0.00370 AC: 121 AN: 32726

American (AMR) AF: 0.00233 AC: 28 AN: 12026

Ashkenazi Jewish (ASJ) AF: 0.000622 AC: 2 AN: 3214

East Asian (EAS) AF: 0.00750 AC: 32 AN: 4266

South Asian (SAS) AF: 0.00282 AC: 11 AN: 3896

European-Finnish (FIN) AF: 0.000312 AC: 2 AN: 6406

Middle Eastern (MID) AF: 0.00417 AC: 1 AN: 240

European-Non Finnish (NFE) AF: 0.00123 AC: 77 AN: 62376

Other (OTH) AF: 0.00517 AC: 9 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

Splicing

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

Other links and lift over

dbSNP: rs376566294; hg19: chr3-186938284;