3-187253508-A-G

Position:

• chr3-187253508-A-G

Variant summary

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

The NM_139125.4(MASP1):​c.745-193T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 151,850 control chromosomes in the GnomAD database, including 11,448 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.36 (11448 hom., cov: 31)
• Consequence: MASP1 NM_139125.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.333

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-187253508-A-G is Benign according to our data. Variant chr3-187253508-A-G is described in ClinVar as [Benign]. Clinvar id is 1276770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MASP1	NM_139125.4	c.745-193T>C		intron_variant		ENST00000296280.11	NP_624302.1
MASP1	NM_001879.6	c.745-193T>C		intron_variant		ENST00000337774.10	NP_001870.3
MASP1	NM_001031849.3	c.745-193T>C		intron_variant			NP_001027019.1
MASP1	NR_033519.2	n.618-193T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MASP1	ENST00000296280.11	c.745-193T>C		intron_variant		1	NM_139125.4	ENSP00000296280.7
MASP1	ENST00000337774.10	c.745-193T>C		intron_variant		1	NM_001879.6	ENSP00000336792.5

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53836 AN: 151732 Hom.: 11423 Cov.: 31

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.355 AC: 53912 AN: 151850 Hom.: 11448 Cov.: 31 AF XY: 0.352 AC XY: 26098 AN XY: 74208

Gnomad4 AFR AF: 0.598

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.332

Alfa AF: 0.265 Hom.: 7658

Bravo AF: 0.367

Asia WGS AF: 0.237 AC: 827 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 16, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.71
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3105782; hg19: chr3-186971296;