rs45602536

Positions:

• chr10-52771730-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001378373.1(MBL2):​c.-9-86C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 1,487,464 control chromosomes in the GnomAD database, including 293 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 0.017 (24 hom., cov: 33)
  • Exomes 𝑓: 0.017 (269 hom.)
• Consequence: MBL2 NM_001378373.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211

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=-0.86).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0172 (2625/152294) while in subpopulation SAS AF= 0.0328 (158/4824). AF 95% confidence interval is 0.0286. There are 24 homozygotes in gnomad4. There are 1255 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2625 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBL2	NM_001378373.1	c.-9-86C>A		intron_variant		ENST00000674931.1	NP_001365302.1
MBL2	NM_001378374.1	c.-24-71C>A		intron_variant			NP_001365303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBL2	ENST00000674931.1	c.-9-86C>A		intron_variant			NM_001378373.1	ENSP00000502789.1
MBL2	ENST00000675947.1	c.-24-71C>A		intron_variant				ENSP00000502615.1
MBL2	ENST00000373968.3	c.-95C>A		upstream_gene_variant		1		ENSP00000363079.3

Frequencies

GnomAD3 genomes AF: 0.0173 AC: 2627 AN: 152176 Hom.: 24 Cov.: 33

Gnomad AFR AF: 0.0227

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0331

Gnomad FIN AF: 0.00687

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0163

Gnomad OTH AF: 0.0177

GnomAD4 exome AF: 0.0172 AC: 23001 AN: 1335170 Hom.: 269 Cov.: 30 AF XY: 0.0176 AC XY: 11487 AN XY: 650918

Gnomad4 AFR exome AF: 0.0216

Gnomad4 AMR exome AF: 0.00844

Gnomad4 ASJ exome AF: 0.0169

Gnomad4 EAS exome AF: 0.0000567

Gnomad4 SAS exome AF: 0.0310

Gnomad4 FIN exome AF: 0.00931

Gnomad4 NFE exome AF: 0.0175

Gnomad4 OTH exome AF: 0.0154

GnomAD4 genome AF: 0.0172 AC: 2625 AN: 152294 Hom.: 24 Cov.: 33 AF XY: 0.0169 AC XY: 1255 AN XY: 74476

Gnomad4 AFR AF: 0.0226

Gnomad4 AMR AF: 0.0139

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0328

Gnomad4 FIN AF: 0.00687

Gnomad4 NFE AF: 0.0163

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0173 Hom.: 2

Bravo AF: 0.0178

Asia WGS AF: 0.0170 AC: 59 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	2.3
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs45602536; hg19: chr10-54531490;