10-52769720-G-A

Variant names:

• chr10-52769720-G-A
• rs10824793
• NM_001378373.1:c.305-405C>T

Variant summary

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

The NM_001378373.1(MBL2):​c.305-405C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,010 control chromosomes in the GnomAD database, including 19,972 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 0.49 (19972 hom., cov: 32)
• Consequence: MBL2 NM_001378373.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493
• Publications: 15 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBL2	NM_001378373.1	c.305-405C>T		intron_variant	Intron 3 of 4	ENST00000674931.1	NP_001365302.1
MBL2	NM_000242.3	c.305-405C>T		intron_variant	Intron 2 of 3		NP_000233.1
MBL2	NM_001378374.1	c.305-405C>T		intron_variant	Intron 3 of 4		NP_001365303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBL2	ENST00000674931.1	c.305-405C>T		intron_variant	Intron 3 of 4		NM_001378373.1	ENSP00000502789.1
MBL2	ENST00000373968.3	c.305-405C>T		intron_variant	Intron 2 of 3	1		ENSP00000363079.3
MBL2	ENST00000675947.1	c.305-405C>T		intron_variant	Intron 3 of 4			ENSP00000502615.1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74754 AN: 151892 Hom.: 19949 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.492 AC: 74803 AN: 152010 Hom.: 19972 Cov.: 32 AF XY: 0.499 AC XY: 37075 AN XY: 74310

African (AFR) AF: 0.266 AC: 11021 AN: 41466

American (AMR) AF: 0.625 AC: 9550 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2002 AN: 3460

East Asian (EAS) AF: 0.648 AC: 3343 AN: 5162

South Asian (SAS) AF: 0.493 AC: 2372 AN: 4808

European-Finnish (FIN) AF: 0.618 AC: 6526 AN: 10560

Middle Eastern (MID) AF: 0.507 AC: 148 AN: 292

European-Non Finnish (NFE) AF: 0.560 AC: 38067 AN: 67968

Other (OTH) AF: 0.518 AC: 1093 AN: 2112

Alfa AF: 0.527 Hom.: 4864

Bravo AF: 0.488

Asia WGS AF: 0.592 AC: 2058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.78
DANN	Benign	0.73
PhyloP100		-0.49
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: rs10824793; hg19: chr10-54529480;