3-187220496-CTTTTTTTTTTTT-CTTTTTTTTTTTTT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001879.6(MASP1):​c.1910-236dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 127,660 control chromosomes in the GnomAD database, including 4,408 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (4408 hom., cov: 22)
• Consequence: MASP1 NM_001879.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 3-187220496-C-CT is Benign according to our data. Variant chr3-187220496-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1230993.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

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.1910-236dupA		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_1910-235insA		intron	N/A	ENSP00000336792.5	P48740-1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 28099 AN: 127674 Hom.: 4405 Cov.: 22

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.0736

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.220 AC: 28106 AN: 127660 Hom.: 4408 Cov.: 22 AF XY: 0.219 AC XY: 13307 AN XY: 60760

African (AFR) AF: 0.379 AC: 12392 AN: 32704

American (AMR) AF: 0.220 AC: 2643 AN: 12024

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 481 AN: 3214

East Asian (EAS) AF: 0.409 AC: 1743 AN: 4260

South Asian (SAS) AF: 0.260 AC: 1008 AN: 3884

European-Finnish (FIN) AF: 0.0736 AC: 471 AN: 6400

Middle Eastern (MID) AF: 0.239 AC: 57 AN: 238

European-Non Finnish (NFE) AF: 0.140 AC: 8729 AN: 62360

Other (OTH) AF: 0.242 AC: 419 AN: 1732

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.67
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: rs376566294; hg19: chr3-186938284; COSMIC: COSV107428103;