rs10824792

Variant names:

• chr10-52766446-C-T
• rs10824792
• NM_001378373.1:c.*1691G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378373.1(MBL2):​c.*1691G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,818 control chromosomes in the GnomAD database, including 20,132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (20132 hom., cov: 31)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: MBL2 NM_001378373.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.460
• Publications: 31 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 10-52766446-C-T is Benign according to our data. Variant chr10-52766446-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 300124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378373.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBL2	NM_001378373.1	MANE Select	c.*1691G>A		3_prime_UTR	Exon 5 of 5	NP_001365302.1	P11226
	MBL2	NM_000242.3		c.*1691G>A		3_prime_UTR	Exon 4 of 4	NP_000233.1	P11226
	MBL2	NM_001378374.1		c.*1691G>A		3_prime_UTR	Exon 5 of 5	NP_001365303.1	P11226

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBL2	ENST00000674931.1	MANE Select	c.*1691G>A		3_prime_UTR	Exon 5 of 5	ENSP00000502789.1	P11226
	MBL2	ENST00000373968.3	TSL:1	c.*1691G>A		3_prime_UTR	Exon 4 of 4	ENSP00000363079.3	P11226
	MBL2	ENST00000675947.1		c.*1691G>A		3_prime_UTR	Exon 5 of 5	ENSP00000502615.1	P11226

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73424 AN: 151698 Hom.: 20124 Cov.: 31

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.492

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.484 AC: 73446 AN: 151816 Hom.: 20132 Cov.: 31 AF XY: 0.489 AC XY: 36282 AN XY: 74220

African (AFR) AF: 0.206 AC: 8529 AN: 41392

American (AMR) AF: 0.605 AC: 9230 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2190 AN: 3456

East Asian (EAS) AF: 0.587 AC: 3032 AN: 5164

South Asian (SAS) AF: 0.553 AC: 2652 AN: 4794

European-Finnish (FIN) AF: 0.580 AC: 6119 AN: 10544

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39889 AN: 67892

Other (OTH) AF: 0.496 AC: 1046 AN: 2110

Alfa AF: 0.562 Hom.: 97237

Bravo AF: 0.475

Asia WGS AF: 0.574 AC: 1992 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Mannose-binding lectin deficiency (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.81
DANN	Benign	0.62
PhyloP100		-0.46
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: rs10824792; hg19: chr10-54526206;