chr3-187219780-A-G

Position:

• chr3-187219780-A-G

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.*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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MASP1	NM_001879.6	c.*291T>C		3_prime_UTR_variant	16/16	ENST00000337774.10	NP_001870.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MASP1	ENST00000337774.10	c.*291T>C		3_prime_UTR_variant	16/16	1	NM_001879.6	ENSP00000336792	P1

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

Gnomad4 AFR exome AF: 0.367

Gnomad4 AMR exome AF: 0.634

Gnomad4 ASJ exome AF: 0.544

Gnomad4 EAS exome AF: 0.880

Gnomad4 SAS exome AF: 0.646

Gnomad4 FIN exome AF: 0.631

Gnomad4 NFE exome AF: 0.574

Gnomad4 OTH exome AF: 0.577

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

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.610

Gnomad4 ASJ AF: 0.555

Gnomad4 EAS AF: 0.872

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.558

Alfa AF: 0.515 Hom.: 4876

Bravo AF: 0.531

Asia WGS AF: 0.723 AC: 2514 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	Mar 31, 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	-0.82
CADD	Benign	0.42
DANN	Benign	0.51

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: rs17040; hg19: chr3-186937568;