3-187223009-G-T

Position:

• chr3-187223009-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001879.6(MASP1):​c.1809+118C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0686 in 870,886 control chromosomes in the GnomAD database, including 3,813 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.088 (896 hom., cov: 32)
  • Exomes 𝑓: 0.064 (2917 hom.)
• Consequence: MASP1 NM_001879.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.155

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]

LOC105374260 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-187223009-G-T is Benign according to our data. Variant chr3-187223009-G-T is described in ClinVar as [Benign]. Clinvar id is 1290828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MASP1	NM_001879.6	c.1809+118C>A		intron_variant		ENST00000337774.10	NP_001870.3
LOC105374260	XR_007096209.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MASP1	ENST00000337774.10	c.1809+118C>A		intron_variant		1	NM_001879.6	ENSP00000336792	P1

Frequencies

GnomAD3 genomes AF: 0.0878 AC: 13344 AN: 152018 Hom.: 889 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0522

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0696

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0338

Gnomad OTH AF: 0.0892

GnomAD4 exome AF: 0.0645 AC: 46327 AN: 718750 Hom.: 2917 AF XY: 0.0638 AC XY: 24348 AN XY: 381830

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.174

Gnomad4 ASJ exome AF: 0.0496

Gnomad4 EAS exome AF: 0.242

Gnomad4 SAS exome AF: 0.0976

Gnomad4 FIN exome AF: 0.0728

Gnomad4 NFE exome AF: 0.0322

Gnomad4 OTH exome AF: 0.0634

GnomAD4 genome AF: 0.0880 AC: 13382 AN: 152136 Hom.: 896 Cov.: 32 AF XY: 0.0909 AC XY: 6757 AN XY: 74374

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0522

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.0696

Gnomad4 NFE AF: 0.0338

Gnomad4 OTH AF: 0.0939

Alfa AF: 0.0542 Hom.: 135

Bravo AF: 0.0966

Asia WGS AF: 0.162 AC: 564 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 16, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.60
DANN	Benign	0.46

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: rs2287366; hg19: chr3-186940797; COSMIC: COSV61826063; COSMIC: COSV61826063;