rs3105782

Variant names:

• chr3-187253508-A-G
• rs3105782
• NM_139125.4:c.745-193T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-187253508-A-G
• chr3-187253508-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• 3MC syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MASP1	NM_139125.4	c.745-193T>C		intron_variant	Intron 5 of 10	ENST00000296280.11	NP_624302.1
MASP1	NM_001879.6	c.745-193T>C		intron_variant	Intron 5 of 15	ENST00000337774.10	NP_001870.3
MASP1	NM_001031849.3	c.745-193T>C		intron_variant	Intron 5 of 8		NP_001027019.1
MASP1	NR_033519.2	n.618-193T>C		intron_variant	Intron 4 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MASP1	ENST00000296280.11	c.745-193T>C		intron_variant	Intron 5 of 10	1	NM_139125.4	ENSP00000296280.7
MASP1	ENST00000337774.10	c.745-193T>C		intron_variant	Intron 5 of 15	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

African (AFR) AF: 0.598 AC: 24765 AN: 41414

American (AMR) AF: 0.311 AC: 4749 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 904 AN: 3468

East Asian (EAS) AF: 0.189 AC: 972 AN: 5152

South Asian (SAS) AF: 0.198 AC: 946 AN: 4778

European-Finnish (FIN) AF: 0.298 AC: 3142 AN: 10538

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17508 AN: 67938

Other (OTH) AF: 0.332 AC: 699 AN: 2108

Alfa AF: 0.278 Hom.: 10882

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 16, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.71
DANN	Benign	0.45
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3105782; hg19: chr3-186971296;