rs930509

Positions:

• chr10-52768593-C-G
• chr10-52768593-C-T

Variant summary

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

The NM_001378373.1(MBL2):​c.374-83G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 1,005,892 control chromosomes in the GnomAD database, including 326,851 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 0.84 (53499 hom., cov: 33)
  • Exomes 𝑓: 0.80 (273352 hom.)
• Consequence: MBL2 NM_001378373.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.793

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBL2	NM_001378373.1	c.374-83G>C		intron_variant		ENST00000674931.1	NP_001365302.1
MBL2	NM_000242.3	c.374-83G>C		intron_variant			NP_000233.1
MBL2	NM_001378374.1	c.374-83G>C		intron_variant			NP_001365303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBL2	ENST00000674931.1	c.374-83G>C		intron_variant			NM_001378373.1	ENSP00000502789	P1
MBL2	ENST00000373968.3	c.374-83G>C		intron_variant		1		ENSP00000363079	P1
MBL2	ENST00000675947.1	c.374-83G>C		intron_variant				ENSP00000502615	P1

Frequencies

GnomAD3 genomes AF: 0.838 AC: 127201 AN: 151868 Hom.: 53444 Cov.: 33

Gnomad AFR AF: 0.883

Gnomad AMI AF: 0.939

Gnomad AMR AF: 0.881

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.812

Gnomad OTH AF: 0.823

GnomAD4 exome AF: 0.799 AC: 682290 AN: 853906 Hom.: 273352 AF XY: 0.798 AC XY: 343790 AN XY: 431000

Gnomad4 AFR exome AF: 0.877

Gnomad4 AMR exome AF: 0.903

Gnomad4 ASJ exome AF: 0.852

Gnomad4 EAS exome AF: 0.869

Gnomad4 SAS exome AF: 0.742

Gnomad4 FIN exome AF: 0.793

Gnomad4 NFE exome AF: 0.792

Gnomad4 OTH exome AF: 0.809

GnomAD4 genome AF: 0.838 AC: 127316 AN: 151986 Hom.: 53499 Cov.: 33 AF XY: 0.838 AC XY: 62229 AN XY: 74294

Gnomad4 AFR AF: 0.883

Gnomad4 AMR AF: 0.881

Gnomad4 ASJ AF: 0.854

Gnomad4 EAS AF: 0.842

Gnomad4 SAS AF: 0.751

Gnomad4 FIN AF: 0.791

Gnomad4 NFE AF: 0.812

Gnomad4 OTH AF: 0.825

Alfa AF: 0.748 Hom.: 2162

Bravo AF: 0.851

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.68

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: rs930509; hg19: chr10-54528353;