10-52768538-G-C

Variant names:

• chr10-52768538-G-C
• rs930508
• NM_001378373.1:c.374-28C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378373.1(MBL2):​c.374-28C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 1,493,554 control chromosomes in the GnomAD database, including 491,055 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.77 (45641 hom., cov: 32)
  • Exomes 𝑓: 0.81 (445414 hom.)
• Consequence: MBL2 NM_001378373.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• Publications: 24 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 -12 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBL2	NM_001378373.1	c.374-28C>G		intron_variant	Intron 4 of 4	ENST00000674931.1	NP_001365302.1
MBL2	NM_000242.3	c.374-28C>G		intron_variant	Intron 3 of 3		NP_000233.1
MBL2	NM_001378374.1	c.374-28C>G		intron_variant	Intron 4 of 4		NP_001365303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBL2	ENST00000674931.1	c.374-28C>G		intron_variant	Intron 4 of 4		NM_001378373.1	ENSP00000502789.1
MBL2	ENST00000373968.3	c.374-28C>G		intron_variant	Intron 3 of 3	1		ENSP00000363079.3
MBL2	ENST00000675947.1	c.374-28C>G		intron_variant	Intron 4 of 4			ENSP00000502615.1

Frequencies

GnomAD3 genomes AF: 0.770 AC: 116884 AN: 151778 Hom.: 45600 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.938

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.850

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.752

Gnomad NFE AF: 0.812

Gnomad OTH AF: 0.773

GnomAD2 exomes AF: 0.796 AC: 137094 AN: 172220 AF XY: 0.795

Gnomad AFR exome AF: 0.650

Gnomad AMR exome AF: 0.883

Gnomad ASJ exome AF: 0.867

Gnomad EAS exome AF: 0.752

Gnomad FIN exome AF: 0.787

Gnomad NFE exome AF: 0.815

Gnomad OTH exome AF: 0.810

GnomAD4 exome AF: 0.813 AC: 1090930 AN: 1341658 Hom.: 445414 Cov.: 25 AF XY: 0.812 AC XY: 535170 AN XY: 659360

African (AFR) AF: 0.653 AC: 19395 AN: 29702

American (AMR) AF: 0.873 AC: 24584 AN: 28176

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 16900 AN: 19716

East Asian (EAS) AF: 0.789 AC: 30465 AN: 38600

South Asian (SAS) AF: 0.751 AC: 51723 AN: 68864

European-Finnish (FIN) AF: 0.791 AC: 38582 AN: 48780

Middle Eastern (MID) AF: 0.747 AC: 3933 AN: 5264

European-Non Finnish (NFE) AF: 0.822 AC: 860807 AN: 1047214

Other (OTH) AF: 0.805 AC: 44541 AN: 55342

GnomAD4 genome AF: 0.770 AC: 116970 AN: 151896 Hom.: 45641 Cov.: 32 AF XY: 0.771 AC XY: 57223 AN XY: 74228

African (AFR) AF: 0.663 AC: 27370 AN: 41270

American (AMR) AF: 0.838 AC: 12805 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.850 AC: 2943 AN: 3462

East Asian (EAS) AF: 0.764 AC: 3951 AN: 5172

South Asian (SAS) AF: 0.747 AC: 3600 AN: 4822

European-Finnish (FIN) AF: 0.788 AC: 8336 AN: 10578

Middle Eastern (MID) AF: 0.771 AC: 225 AN: 292

European-Non Finnish (NFE) AF: 0.812 AC: 55251 AN: 68008

Other (OTH) AF: 0.776 AC: 1635 AN: 2108

Alfa AF: 0.782 Hom.: 6328

Bravo AF: 0.772

Asia WGS AF: 0.775 AC: 2695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.35
PhyloP100		0.13
BranchPoint Hunter		0.0
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: rs930508; hg19: chr10-54528298; COSMIC: COSV107495044;