10-52771339-C-T

Variant names:

• chr10-52771339-C-T
• rs4647964
• NM_001378373.1:c.187+110G>A

Variant summary

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

The NM_001378373.1(MBL2):​c.187+110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,198,142 control chromosomes in the GnomAD database, including 36,761 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 (7891 hom., cov: 32)
  • Exomes 𝑓: 0.23 (28870 hom.)
• Consequence: MBL2 NM_001378373.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.687
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378373.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBL2	NM_001378373.1	MANE Select	c.187+110G>A		intron	N/A	NP_001365302.1
	MBL2	NM_000242.3		c.187+110G>A		intron	N/A	NP_000233.1
	MBL2	NM_001378374.1		c.187+110G>A		intron	N/A	NP_001365303.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBL2	ENST00000674931.1	MANE Select	c.187+110G>A		intron	N/A	ENSP00000502789.1
	MBL2	ENST00000373968.3	TSL:1	c.187+110G>A		intron	N/A	ENSP00000363079.3
	MBL2	ENST00000675947.1		c.187+110G>A		intron	N/A	ENSP00000502615.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44484 AN: 151990 Hom.: 7878 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: 0.137

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.270

GnomAD4 exome AF: 0.228 AC: 238551 AN: 1046034 Hom.: 28870 AF XY: 0.228 AC XY: 118431 AN XY: 519122

African (AFR) AF: 0.519 AC: 12531 AN: 24132

American (AMR) AF: 0.174 AC: 4403 AN: 25260

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 4578 AN: 17260

East Asian (EAS) AF: 0.139 AC: 5068 AN: 36540

South Asian (SAS) AF: 0.244 AC: 14195 AN: 58092

European-Finnish (FIN) AF: 0.173 AC: 8187 AN: 47190

Middle Eastern (MID) AF: 0.233 AC: 705 AN: 3030

European-Non Finnish (NFE) AF: 0.226 AC: 178397 AN: 789178

Other (OTH) AF: 0.231 AC: 10487 AN: 45352

GnomAD4 genome AF: 0.293 AC: 44530 AN: 152108 Hom.: 7891 Cov.: 32 AF XY: 0.288 AC XY: 21431 AN XY: 74380

African (AFR) AF: 0.508 AC: 21056 AN: 41454

American (AMR) AF: 0.212 AC: 3240 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 910 AN: 3462

East Asian (EAS) AF: 0.137 AC: 710 AN: 5176

South Asian (SAS) AF: 0.246 AC: 1186 AN: 4828

European-Finnish (FIN) AF: 0.175 AC: 1854 AN: 10596

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

European-Non Finnish (NFE) AF: 0.217 AC: 14757 AN: 68004

Other (OTH) AF: 0.267 AC: 564 AN: 2116

Alfa AF: 0.250 Hom.: 1859

Bravo AF: 0.303

Asia WGS AF: 0.186 AC: 648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.17
DANN	Benign	0.19
PhyloP100		-0.69
PromoterAI		-0.024	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4647964; hg19: chr10-54531099;