chr3-187220446-C-A

Variant names:

• chr3-187220446-C-A
• rs73191704
• NM_001879.6:c.1910-185G>T

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.1910-185G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 152,086 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.011 (11 hom., cov: 32)
• Consequence: MASP1 NM_001879.6 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.64
• 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=-0.98).
• BP6: Variant 3-187220446-C-A is Benign according to our data. Variant chr3-187220446-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1204572.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0109 (1665/152086) while in subpopulation NFE AF = 0.0163 (1107/67990). AF 95% confidence interval is 0.0155. There are 11 homozygotes in GnomAd4. There are 789 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 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.1910-185G>T		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.1910-185G>T		intron	N/A	ENSP00000336792.5	P48740-1

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1666 AN: 151968 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00302

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00924

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00939

Gnomad FIN AF: 0.0192

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0163

Gnomad OTH AF: 0.0130

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

GnomAD4 genome AF: 0.0109 AC: 1665 AN: 152086 Hom.: 11 Cov.: 32 AF XY: 0.0106 AC XY: 789 AN XY: 74348

African (AFR) AF: 0.00301 AC: 125 AN: 41516

American (AMR) AF: 0.00923 AC: 141 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00919 AC: 44 AN: 4790

European-Finnish (FIN) AF: 0.0192 AC: 203 AN: 10554

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0163 AC: 1107 AN: 67990

Other (OTH) AF: 0.0128 AC: 27 AN: 2104

Alfa AF: 0.00457 Hom.: 1

Bravo AF: 0.00994

Asia WGS AF: 0.00289 AC: 11 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	-0.98
CADD	Benign	0.010
DANN	Benign	0.48
PhyloP100		-2.6
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: rs73191704; hg19: chr3-186938234;