3-187219780-A-G

Variant names:

• chr3-187219780-A-G
• rs17040
• NM_001879.6:c.*291T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001879.6(MASP1):​c.*291T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 466,450 control chromosomes in the GnomAD database, including 81,611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (23372 hom., cov: 32)
  • Exomes 𝑓: 0.60 (58239 hom.)
• Consequence: MASP1 NM_001879.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.346
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-187219780-A-G is Benign according to our data. Variant chr3-187219780-A-G is described in ClinVar as Benign. ClinVar VariationId is 1244207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 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.*291T>C		3_prime_UTR	Exon 16 of 16	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.*291T>C		3_prime_UTR	Exon 16 of 16	ENSP00000336792.5	P48740-1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82280 AN: 151898 Hom.: 23357 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.557

GnomAD4 exome AF: 0.600 AC: 188745 AN: 314434 Hom.: 58239 Cov.: 2 AF XY: 0.604 AC XY: 100356 AN XY: 166286

African (AFR) AF: 0.367 AC: 3506 AN: 9564

American (AMR) AF: 0.634 AC: 9238 AN: 14568

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 5157 AN: 9478

East Asian (EAS) AF: 0.880 AC: 16330 AN: 18548

South Asian (SAS) AF: 0.646 AC: 27319 AN: 42302

European-Finnish (FIN) AF: 0.631 AC: 10685 AN: 16932

Middle Eastern (MID) AF: 0.558 AC: 743 AN: 1332

European-Non Finnish (NFE) AF: 0.574 AC: 105538 AN: 183982

Other (OTH) AF: 0.577 AC: 10229 AN: 17728

GnomAD4 genome AF: 0.542 AC: 82342 AN: 152016 Hom.: 23372 Cov.: 32 AF XY: 0.549 AC XY: 40807 AN XY: 74296

African (AFR) AF: 0.376 AC: 15569 AN: 41436

American (AMR) AF: 0.610 AC: 9317 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1926 AN: 3468

East Asian (EAS) AF: 0.872 AC: 4515 AN: 5176

South Asian (SAS) AF: 0.666 AC: 3208 AN: 4820

European-Finnish (FIN) AF: 0.633 AC: 6693 AN: 10568

Middle Eastern (MID) AF: 0.531 AC: 155 AN: 292

European-Non Finnish (NFE) AF: 0.579 AC: 39363 AN: 67952

Other (OTH) AF: 0.558 AC: 1179 AN: 2114

Alfa AF: 0.545 Hom.: 9441

Bravo AF: 0.531

Asia WGS AF: 0.723 AC: 2514 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: 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	-0.82
CADD	Benign	0.42
DANN	Benign	0.51
PhyloP100		-0.35
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: rs17040; hg19: chr3-186937568;