rs11003124

Variant names:

• chr10-52772131-T-G
• rs11003124
• NM_001378373.1:c.-9-487A>C

Variant summary

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

The NM_001378373.1(MBL2):​c.-9-487A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,056 control chromosomes in the GnomAD database, including 7,881 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 0.29 (7881 hom., cov: 32)
• Consequence: MBL2 NM_001378373.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195
• Publications: 16 publications found

Genes affected

MBL2 (HGNC:6922): (mannose binding lectin 2) This gene encodes the soluble mannose-binding lectin or mannose-binding protein found in serum. The protein encoded belongs to the collectin family and is an important element in the innate immune system. The protein recognizes and binds to mannose and N-acetylglucosamine on many microorganisms, including bacteria, yeast, and viruses including influenza virus, HIV and SARS-CoV. This binding activates the classical complement pathway. Deficiencies of this gene have been associated with susceptibility to autoimmune and infectious diseases. [provided by RefSeq, Jun 2020]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBL2	NM_001378373.1	c.-9-487A>C		intron_variant	Intron 1 of 4	ENST00000674931.1	NP_001365302.1
MBL2	NM_001378374.1	c.-24-472A>C		intron_variant	Intron 1 of 4		NP_001365303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBL2	ENST00000674931.1	c.-9-487A>C		intron_variant	Intron 1 of 4		NM_001378373.1	ENSP00000502789.1
MBL2	ENST00000675947.1	c.-24-472A>C		intron_variant	Intron 1 of 4			ENSP00000502615.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44435 AN: 151938 Hom.: 7868 Cov.: 32

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.293 AC: 44480 AN: 152056 Hom.: 7881 Cov.: 32 AF XY: 0.288 AC XY: 21393 AN XY: 74328

African (AFR) AF: 0.508 AC: 21039 AN: 41440

American (AMR) AF: 0.212 AC: 3249 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 912 AN: 3462

East Asian (EAS) AF: 0.134 AC: 692 AN: 5162

South Asian (SAS) AF: 0.245 AC: 1180 AN: 4818

European-Finnish (FIN) AF: 0.174 AC: 1841 AN: 10578

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14751 AN: 67990

Other (OTH) AF: 0.267 AC: 563 AN: 2108

Alfa AF: 0.264 Hom.: 823

Bravo AF: 0.303

Asia WGS AF: 0.186 AC: 647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.71
DANN	Benign	0.70
PhyloP100		-0.20
PromoterAI		0.015	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11003124; hg19: chr10-54531891;