10-52769945-C-T

Variant names:

• chr10-52769945-C-T
• rs4935046
• NM_001378373.1:c.305-630G>A

Variant summary

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

The NM_001378373.1(MBL2):​c.305-630G>A 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 152,098 control chromosomes in the GnomAD database, including 19,936 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 (19936 hom., cov: 33)
• Consequence: MBL2 NM_001378373.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBL2	NM_001378373.1	c.305-630G>A		intron_variant	Intron 3 of 4	ENST00000674931.1	NP_001365302.1
MBL2	NM_000242.3	c.305-630G>A		intron_variant	Intron 2 of 3		NP_000233.1
MBL2	NM_001378374.1	c.305-630G>A		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.305-630G>A		intron_variant	Intron 3 of 4		NM_001378373.1	ENSP00000502789.1
MBL2	ENST00000373968.3	c.305-630G>A		intron_variant	Intron 2 of 3	1		ENSP00000363079.3
MBL2	ENST00000675947.1	c.305-630G>A		intron_variant	Intron 3 of 4			ENSP00000502615.1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74713 AN: 151980 Hom.: 19913 Cov.: 33

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.487

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: 74762 AN: 152098 Hom.: 19936 Cov.: 33 AF XY: 0.498 AC XY: 37054 AN XY: 74346

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.625

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.638

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.518

Alfa AF: 0.519 Hom.: 2670

Bravo AF: 0.488

Asia WGS AF: 0.589 AC: 2051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.20
DANN	Benign	0.75

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: rs4935046; hg19: chr10-54529705;