rs72549155

Positions:

• chr3-187236187-G-C
• chr3-187236187-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_139125.4(MASP1):​c.1684C>G​(p.Pro562Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000187 in 1,614,124 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00029 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00018 (3 hom.)
• Consequence: MASP1 NM_139125.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.774

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01251477).
• BP6: Variant 3-187236187-G-C is Benign according to our data. Variant chr3-187236187-G-C is described in ClinVar as [Benign]. Clinvar id is 707092.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000289 (44/152342) while in subpopulation EAS AF= 0.00328 (17/5180). AF 95% confidence interval is 0.00209. There are 1 homozygotes in gnomad4. There are 24 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MASP1	NM_139125.4	c.1684C>G	p.Pro562Ala	missense_variant	11/11	ENST00000296280.11	NP_624302.1
MASP1	NM_001879.6	c.1303+5294C>G		intron_variant		ENST00000337774.10	NP_001870.3
MASP1	NR_033519.2	n.1557C>G		non_coding_transcript_exon_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MASP1	ENST00000296280.11	c.1684C>G	p.Pro562Ala	missense_variant	11/11	1	NM_139125.4	ENSP00000296280.7
MASP1	ENST00000337774.10	c.1303+5294C>G		intron_variant		1	NM_001879.6	ENSP00000336792.5

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 44 AN: 152224 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000398 AC: 100 AN: 251236 Hom.: 2 AF XY: 0.000442 AC XY: 60 AN XY: 135826

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00299

Gnomad SAS exome AF: 0.000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000176 AC: 258 AN: 1461782 Hom.: 3 Cov.: 81 AF XY: 0.000212 AC XY: 154 AN XY: 727196

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000470

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00239

Gnomad4 SAS exome AF: 0.00133

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000117

Gnomad4 OTH exome AF: 0.000182

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152342 Hom.: 1 Cov.: 33 AF XY: 0.000322 AC XY: 24 AN XY: 74486

Gnomad4 AFR AF: 0.0000240

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.0000854 Hom.: 0

Bravo AF: 0.000472

ExAC AF: 0.000404 AC: 49

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	13
DANN	Benign	0.84
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.53	T;T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.013	T;T
MetaSVM	Uncertain	-0.013	T
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.5	N;N
REVEL	Uncertain	0.31
Sift	Benign	0.42	T;T
Sift4G	Benign	0.66	T;T
Polyphen		0.0010	B;B
Vest4		0.17
MVP		0.90
MPC		0.12
ClinPred		0.0062	T
GERP RS		5.2
gMVP		0.38

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

Other links and lift over

dbSNP: rs72549155; hg19: chr3-186953975;