rs28945068

Positions:

chr3-187241507-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_139125.4(MASP1):c.1277G>A(p.Gly426Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 1,613,460 control chromosomes in the GnomAD database, including 234 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 13 hom., cov: 32)

Exomes 𝑓: 0.016 ( 221 hom. )

Consequence

MASP1
NM_139125.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.07

Variant links:

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 links:

MASP1 (HGNC:):

MASP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043150485).

BP6

Variant 3-187241507-C-T is Benign according to our data. Variant chr3-187241507-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 463034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-187241507-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0121 (1836/152100) while in subpopulation NFE AF= 0.0178 (1208/67984). AF 95% confidence interval is 0.0169. There are 13 homozygotes in gnomad4. There are 876 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MASP1	NM_139125.4 linkuse as main transcript	c.1277G>A	p.Gly426Glu	missense_variant	10/11	ENST00000296280.11	NP_624302.1	P48740-2
MASP1	NM_001879.6 linkuse as main transcript	c.1277G>A	p.Gly426Glu	missense_variant	10/16	ENST00000337774.10	NP_001870.3	P48740-1
MASP1	NR_033519.2 linkuse as main transcript	n.1150G>A		non_coding_transcript_exon_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MASP1	ENST00000296280.11 linkuse as main transcript	c.1277G>A	p.Gly426Glu	missense_variant	10/11	1	NM_139125.4	ENSP00000296280.7		P48740-2
MASP1	ENST00000337774.10 linkuse as main transcript	c.1277G>A	p.Gly426Glu	missense_variant	10/16	1	NM_001879.6	ENSP00000336792.5		P48740-1

Frequencies

GnomAD3 genomes

AF:

0.0121

AC:

1836

AN:

151982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00302

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0136

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00270

Gnomad FIN

AF:

0.0227

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0178

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.0122

AC:

3072

AN:

251482

Hom.:

AF XY:

0.0122

AC XY:

1658

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00228

Gnomad AMR exome

AF:

0.00934

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00144

Gnomad FIN exome

AF:

0.0236

Gnomad NFE exome

AF:

0.0180

Gnomad OTH exome

AF:

0.0143

GnomAD4 exome

AF:

0.0163

AC:

23840

AN:

1461360

Hom.:

221

Cov.:

AF XY:

0.0157

AC XY:

11429

AN XY:

726998

show subpopulations

Gnomad4 AFR exome

AF:

0.00218

Gnomad4 AMR exome

AF:

0.0103

Gnomad4 ASJ exome

AF:

0.00142

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00179

Gnomad4 FIN exome

AF:

0.0217

Gnomad4 NFE exome

AF:

0.0191

Gnomad4 OTH exome

AF:

0.0125

GnomAD4 genome

AF:

0.0121

AC:

1836

AN:

152100

Hom.:

Cov.:

AF XY:

0.0118

AC XY:

876

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00301

Gnomad4 AMR

AF:

0.0136

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.0227

Gnomad4 NFE

AF:

0.0178

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.0148

Hom.:

Bravo

AF:

0.0107

TwinsUK

AF:

0.0213

AC:

ALSPAC

AF:

0.0213

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.0144

AC:

124

ExAC

AF:

0.0118

AC:

1432

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

3MC syndrome 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 11, 2024	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.23

DEOGEN2

Benign

0.15

T;.;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.51

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.68

T;T;T

MetaRNN

Benign

0.0043

T;T;T

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.1

M;M;.

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-2.6

D;N;D

REVEL

Benign

0.22

Sift

Benign

0.89

T;T;T

Sift4G

Benign

0.37

T;T;T

Polyphen

0.15

B;B;B

Vest4

0.20

MPC

0.18

ClinPred

0.037

GERP RS

3.1

Varity_R

0.37

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over