3-187266730-G-A

Variant names:

• chr3-187266730-G-A
• rs710469
• NM_139125.4:c.238-4010C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139125.4(MASP1):​c.238-4010C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,976 control chromosomes in the GnomAD database, including 17,632 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (17632 hom., cov: 31)
• Consequence: MASP1 NM_139125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139125.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASP1	NM_139125.4	MANE Select	c.238-4010C>T		intron	N/A	NP_624302.1
	MASP1	NM_001879.6	MANE Plus Clinical	c.238-4010C>T		intron	N/A	NP_001870.3
	MASP1	NM_001031849.3		c.238-4010C>T		intron	N/A	NP_001027019.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASP1	ENST00000296280.11	TSL:1 MANE Select	c.238-4010C>T		intron	N/A	ENSP00000296280.7
	MASP1	ENST00000337774.10	TSL:1 MANE Plus Clinical	c.238-4010C>T		intron	N/A	ENSP00000336792.5
	MASP1	ENST00000392472.6	TSL:1	c.-102-4010C>T		intron	N/A	ENSP00000376264.2

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72468 AN: 151856 Hom.: 17618 Cov.: 31

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.477 AC: 72507 AN: 151976 Hom.: 17632 Cov.: 31 AF XY: 0.481 AC XY: 35759 AN XY: 74290

African (AFR) AF: 0.367 AC: 15182 AN: 41424

American (AMR) AF: 0.569 AC: 8700 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1705 AN: 3470

East Asian (EAS) AF: 0.532 AC: 2750 AN: 5168

South Asian (SAS) AF: 0.567 AC: 2728 AN: 4812

European-Finnish (FIN) AF: 0.560 AC: 5918 AN: 10568

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33864 AN: 67946

Other (OTH) AF: 0.478 AC: 1005 AN: 2102

Alfa AF: 0.489 Hom.: 48508

Bravo AF: 0.472

Asia WGS AF: 0.542 AC: 1889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.70
DANN	Benign	0.41
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs710469; hg19: chr3-186984518;