3-187220496-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001879.6(MASP1):c.1910-236_1910-235insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 127,660 control chromosomes in the GnomAD database, including 4,408 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (4408 hom., cov: 22)
• Consequence: MASP1 NM_001879.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.667

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-187220496-C-CT is Benign according to our data. Variant chr3-187220496-C-CT is described in ClinVar as [Benign]. Clinvar id is 1230993.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MASP1	NM_001879.6	c.1910-236_1910-235insA		intron_variant		ENST00000337774.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MASP1	ENST00000337774.10	c.1910-236_1910-235insA		intron_variant		1	NM_001879.6	P1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 28099 AN: 127674 Hom.: 4405 Cov.: 22

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.0736

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.220 AC: 28106 AN: 127660 Hom.: 4408 Cov.: 22 AF XY: 0.219 AC XY: 13307 AN XY: 60760

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.409

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.0736

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.242

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 21, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs376566294; hg19: chr3-186938284;