NM_001879.6:c.1910-239_1910-238insG

Variant names:

• chr3-187220499-T-TC
• rs201621678
• NM_001879.6:c.1910-239_1910-238insG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001879.6(MASP1):​c.1910-239_1910-238insG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00942 in 144,360 control chromosomes in the GnomAD database, including 26 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0094 (26 hom., cov: 30)
• Consequence: MASP1 NM_001879.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.129
• 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 -10 ACMG points.

• BP6: Variant 3-187220499-T-TC is Benign according to our data. Variant chr3-187220499-T-TC is described in ClinVar as Likely_benign. ClinVar VariationId is 1219212.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00942 (1360/144360) while in subpopulation AFR AF = 0.0291 (1139/39154). AF 95% confidence interval is 0.0277. There are 26 homozygotes in GnomAd4. There are 682 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 26 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.1910-239_1910-238insG		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.1910-239_1910-238insG		intron	N/A	ENSP00000336792.5	P48740-1

Frequencies

GnomAD3 genomes AF: 0.00943 AC: 1361 AN: 144276 Hom.: 26 Cov.: 30

Gnomad AFR AF: 0.0291

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00390

Gnomad ASJ AF: 0.000590

Gnomad EAS AF: 0.000794

Gnomad SAS AF: 0.0269

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0128

Gnomad NFE AF: 0.000274

Gnomad OTH AF: 0.0103

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

GnomAD4 genome AF: 0.00942 AC: 1360 AN: 144360 Hom.: 26 Cov.: 30 AF XY: 0.00973 AC XY: 682 AN XY: 70124

African (AFR) AF: 0.0291 AC: 1139 AN: 39154

American (AMR) AF: 0.00389 AC: 57 AN: 14638

Ashkenazi Jewish (ASJ) AF: 0.000590 AC: 2 AN: 3390

East Asian (EAS) AF: 0.000797 AC: 4 AN: 5020

South Asian (SAS) AF: 0.0263 AC: 115 AN: 4376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9046

Middle Eastern (MID) AF: 0.0138 AC: 4 AN: 290

European-Non Finnish (NFE) AF: 0.000274 AC: 18 AN: 65586

Other (OTH) AF: 0.0107 AC: 21 AN: 1960

Alfa AF: 0.00717 Hom.: 0

Asia WGS AF: 0.0130 AC: 47 AN: 3442

ClinVar

ClinVar submissions

Significance: Likely 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		0.13
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: rs201621678; hg19: chr3-186938287;