NM_139125.4:c.6-575T>C

Variant names:

• chr3-187286631-A-G
• rs698106
• NM_139125.4:c.6-575T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139125.4(MASP1):​c.6-575T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 152,196 control chromosomes in the GnomAD database, including 45,850 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 0.76 (45850 hom., cov: 33)
• Consequence: MASP1 NM_139125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.441
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139125.4. 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_139125.4	MANE Select	c.6-575T>C		intron	N/A	NP_624302.1	P48740-2
	MASP1	NM_001879.6	MANE Plus Clinical	c.6-575T>C		intron	N/A	NP_001870.3
	MASP1	NM_001031849.3		c.6-575T>C		intron	N/A	NP_001027019.1	P48740-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASP1	ENST00000296280.11	TSL:1 MANE Select	c.6-575T>C		intron	N/A	ENSP00000296280.7	P48740-2
	MASP1	ENST00000337774.10	TSL:1 MANE Plus Clinical	c.6-575T>C		intron	N/A	ENSP00000336792.5	P48740-1
	MASP1	ENST00000392472.6	TSL:1	c.-103+4997T>C		intron	N/A	ENSP00000376264.2	P48740-4

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116305 AN: 152078 Hom.: 45831 Cov.: 33

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.905

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.753

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

GnomAD4 genome AF: 0.765 AC: 116364 AN: 152196 Hom.: 45850 Cov.: 33 AF XY: 0.767 AC XY: 57062 AN XY: 74420

African (AFR) AF: 0.554 AC: 22964 AN: 41460

American (AMR) AF: 0.808 AC: 12352 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 2928 AN: 3472

East Asian (EAS) AF: 0.885 AC: 4587 AN: 5182

South Asian (SAS) AF: 0.819 AC: 3953 AN: 4826

European-Finnish (FIN) AF: 0.884 AC: 9392 AN: 10620

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.846 AC: 57528 AN: 68018

Other (OTH) AF: 0.754 AC: 1596 AN: 2116

Alfa AF: 0.795 Hom.: 6089

Bravo AF: 0.750

Asia WGS AF: 0.846 AC: 2940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.7
DANN	Benign	0.62
PhyloP100		0.44
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: rs698106; hg19: chr3-187004419;