rs35615810

Positions:

• chr10-52772071-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001378373.1(MBL2):​c.-9-427G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00785 in 152,280 control chromosomes in the GnomAD database, including 7 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 0.0079 (7 hom., cov: 33)
• Consequence: MBL2 NM_001378373.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.767

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BS2: High AC in GnomAd4 at 1196 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBL2	NM_001378373.1	c.-9-427G>T		intron_variant		ENST00000674931.1	NP_001365302.1
MBL2	NM_001378374.1	c.-24-412G>T		intron_variant			NP_001365303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBL2	ENST00000674931.1	c.-9-427G>T		intron_variant			NM_001378373.1	ENSP00000502789	P1
MBL2	ENST00000675947.1	c.-24-412G>T		intron_variant				ENSP00000502615	P1

Frequencies

GnomAD3 genomes AF: 0.00785 AC: 1195 AN: 152162 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00212

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00772

Gnomad ASJ AF: 0.00347

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00858

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0125

Gnomad OTH AF: 0.00717

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

GnomAD4 genome AF: 0.00785 AC: 1196 AN: 152280 Hom.: 7 Cov.: 33 AF XY: 0.00783 AC XY: 583 AN XY: 74440

Gnomad4 AFR AF: 0.00212

Gnomad4 AMR AF: 0.00771

Gnomad4 ASJ AF: 0.00347

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00858

Gnomad4 NFE AF: 0.0125

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00865 Hom.: 1

Bravo AF: 0.00753

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.5
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35615810; hg19: chr10-54531831;