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3-187220446-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001879.6(MASP1):c.1910-185G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 152,086 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.011 ( 11 hom., cov: 32)

Consequence

MASP1
NM_001879.6 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.64
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.98).
BP6
Variant 3-187220446-C-A is Benign according to our data. Variant chr3-187220446-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1204572.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0109 (1665/152086) while in subpopulation NFE AF= 0.0163 (1107/67990). AF 95% confidence interval is 0.0155. There are 11 homozygotes in gnomad4. There are 789 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MASP1NM_001879.6 linkuse as main transcriptc.1910-185G>T intron_variant ENST00000337774.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MASP1ENST00000337774.10 linkuse as main transcriptc.1910-185G>T intron_variant 1 NM_001879.6 P1P48740-1

Frequencies

GnomAD3 genomes
AF:
0.0110
AC:
1666
AN:
151968
Hom.:
11
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00302
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.00924
Gnomad ASJ
AF:
0.00346
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00939
Gnomad FIN
AF:
0.0192
Gnomad MID
AF:
0.0158
Gnomad NFE
AF:
0.0163
Gnomad OTH
AF:
0.0130
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0109
AC:
1665
AN:
152086
Hom.:
11
Cov.:
32
AF XY:
0.0106
AC XY:
789
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.00301
Gnomad4 AMR
AF:
0.00923
Gnomad4 ASJ
AF:
0.00346
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00919
Gnomad4 FIN
AF:
0.0192
Gnomad4 NFE
AF:
0.0163
Gnomad4 OTH
AF:
0.0128
Alfa
AF:
0.00457
Hom.:
1
Bravo
AF:
0.00994
Asia WGS
AF:
0.00289
AC:
11
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxJun 27, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.98
Cadd
Benign
0.010
Dann
Benign
0.48

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

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

Other links and lift over

dbSNP: rs73191704; hg19: chr3-186938234; API