NM_001879.6:c.1909+107G>A

Variant names:

• chr3-187220928-C-T
• rs151279132
• NM_001879.6:c.1909+107G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001879.6(MASP1):​c.1909+107G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 870,548 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0052 (2 hom., cov: 31)
  • Exomes 𝑓: 0.00067 (3 hom.)
• Consequence: MASP1 NM_001879.6 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.425
• 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)
• 3MC syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-187220928-C-T is Benign according to our data. Variant chr3-187220928-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1210531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00524 (798/152340) while in subpopulation AFR AF = 0.0182 (757/41576). AF 95% confidence interval is 0.0171. There are 2 homozygotes in GnomAd4. There are 371 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 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.1909+107G>A		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.1909+107G>A		intron	N/A	ENSP00000336792.5	P48740-1

Frequencies

GnomAD3 genomes AF: 0.00522 AC: 795 AN: 152222 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.0182

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.000674 AC: 484 AN: 718208 Hom.: 3 AF XY: 0.000514 AC XY: 197 AN XY: 382896

African (AFR) AF: 0.0193 AC: 366 AN: 18954

American (AMR) AF: 0.00105 AC: 43 AN: 40854

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21038

East Asian (EAS) AF: 0.0000573 AC: 2 AN: 34910

South Asian (SAS) AF: 0.0000726 AC: 5 AN: 68908

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47906

Middle Eastern (MID) AF: 0.00137 AC: 4 AN: 2922

European-Non Finnish (NFE) AF: 0.0000268 AC: 12 AN: 446944

Other (OTH) AF: 0.00145 AC: 52 AN: 35772

GnomAD4 genome AF: 0.00524 AC: 798 AN: 152340 Hom.: 2 Cov.: 31 AF XY: 0.00498 AC XY: 371 AN XY: 74498

African (AFR) AF: 0.0182 AC: 757 AN: 41576

American (AMR) AF: 0.00202 AC: 31 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00112 Hom.: 0

Bravo AF: 0.00612

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.30
DANN	Benign	0.79
PhyloP100		-0.42
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: rs151279132; hg19: chr3-186938716;