rs7095891

Positions:

• chr10-52771701-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378373.1(MBL2):​c.-9-57C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,535,498 control chromosomes in the GnomAD database, including 46,114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7902 hom., cov: 33)
  • Exomes 𝑓: 0.23 (38212 hom.)
• Consequence: MBL2 NM_001378373.1 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.511

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 10-52771701-G-A is Benign according to our data. Variant chr10-52771701-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 368900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBL2	NM_001378373.1	c.-9-57C>T		intron_variant		ENST00000674931.1	NP_001365302.1
MBL2	NM_001378374.1	c.-24-42C>T		intron_variant			NP_001365303.1
MBL2	NM_000242.3	c.-66C>T		upstream_gene_variant			NP_000233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBL2	ENST00000674931.1	c.-9-57C>T		intron_variant			NM_001378373.1	ENSP00000502789.1
MBL2	ENST00000675947.1	c.-24-42C>T		intron_variant				ENSP00000502615.1
MBL2	ENST00000373968.3	c.-66C>T		upstream_gene_variant		1		ENSP00000363079.3

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44503 AN: 151986 Hom.: 7889 Cov.: 33

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.270

GnomAD4 exome AF: 0.228 AC: 315227 AN: 1383394 Hom.: 38212 Cov.: 32 AF XY: 0.228 AC XY: 154684 AN XY: 679392

Gnomad4 AFR exome AF: 0.522

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.263

Gnomad4 EAS exome AF: 0.138

Gnomad4 SAS exome AF: 0.241

Gnomad4 FIN exome AF: 0.174

Gnomad4 NFE exome AF: 0.225

Gnomad4 OTH exome AF: 0.231

GnomAD4 genome AF: 0.293 AC: 44549 AN: 152104 Hom.: 7902 Cov.: 33 AF XY: 0.288 AC XY: 21441 AN XY: 74356

Gnomad4 AFR AF: 0.508

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.267

Alfa AF: 0.253 Hom.: 997

Bravo AF: 0.303

Asia WGS AF: 0.186 AC: 646 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Mannose-binding lectin deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7095891; hg19: chr10-54531461; COSMIC: COSV64758225;