rs9430176

Variant names:

• chr1-11030974-G-A
• rs9430176
• NM_006610.4:c.1088-92C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-11030974-G-A
• chr1-11030974-G-C
• chr1-11030974-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006610.4(MASP2):​c.1088-92C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.03 in 1,342,370 control chromosomes in the GnomAD database, including 1,579 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 0.046 (330 hom., cov: 31)
  • Exomes 𝑓: 0.028 (1249 hom.)
• Consequence: MASP2 NM_006610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393

Genes affected

MASP2 (HGNC:6902): (MBL associated serine protease 2) This gene encodes a member of the peptidase S1 family of serine proteases. The encoded preproprotein is proteolytically processed to generate A and B chains that heterodimerize to form the mature protease. This protease cleaves complement components C2 and C4 in order to generate C3 convertase in the lectin pathway of the complement system. The encoded protease also plays a role in the coagulation cascade through cleavage of prothrombin to form thrombin. Myocardial infarction and acute stroke patients exhibit reduced serum concentrations of the encoded protein. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MASP2	NM_006610.4	c.1088-92C>T		intron_variant	Intron 8 of 10	ENST00000400897.8	NP_006601.2
MASP2	XR_001736931.1	n.1041-92C>T		intron_variant	Intron 7 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MASP2	ENST00000400897.8	c.1088-92C>T		intron_variant	Intron 8 of 10	1	NM_006610.4	ENSP00000383690.3

Frequencies

GnomAD3 genomes AF: 0.0458 AC: 6958 AN: 151870 Hom.: 332 Cov.: 31

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.0307

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0100

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0187

Gnomad OTH AF: 0.0527

GnomAD4 exome AF: 0.0280 AC: 33320 AN: 1190382 Hom.: 1249 AF XY: 0.0295 AC XY: 17467 AN XY: 592096

Gnomad4 AFR exome AF: 0.0721

Gnomad4 AMR exome AF: 0.0198

Gnomad4 ASJ exome AF: 0.0409

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.0846

Gnomad4 FIN exome AF: 0.00980

Gnomad4 NFE exome AF: 0.0169

Gnomad4 OTH exome AF: 0.0396

GnomAD4 genome AF: 0.0458 AC: 6964 AN: 151988 Hom.: 330 Cov.: 31 AF XY: 0.0472 AC XY: 3506 AN XY: 74292

Gnomad4 AFR AF: 0.0801

Gnomad4 AMR AF: 0.0305

Gnomad4 ASJ AF: 0.0349

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0100

Gnomad4 NFE AF: 0.0187

Gnomad4 OTH AF: 0.0531

Alfa AF: 0.0329 Hom.: 19

Bravo AF: 0.0483

Asia WGS AF: 0.129 AC: 446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.88
DANN	Benign	0.55

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: rs9430176; hg19: chr1-11091031;