dbSNP rs72661131: MBL2:c.-9-95T>C (chr10-52771739-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001378373.1(MBL2):c.-9-95T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000251 in 1,462,400 control chromosomes in the GnomAD database, including 1 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 0.00077 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

MBL2
NM_001378373.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.764

Publications

6 publications found

Variant links:

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]

MBL2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BS2

High AC in GnomAd4 at 118 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MBL2	NM_001378373.1 link	c.-9-95T>C	intron_variant	Intron 1 of 4	ENST00000674931.1	NP_001365302.1
MBL2	NM_001378374.1 link	c.-24-80T>C	intron_variant	Intron 1 of 4		NP_001365303.1
MBL2	NM_000242.3 link	c.-104T>C	upstream_gene_variant			NP_000233.1	P11226

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MBL2	ENST00000674931.1 link	c.-9-95T>C	intron_variant	Intron 1 of 4		NM_001378373.1	ENSP00000502789.1	P11226
MBL2	ENST00000675947.1 link	c.-24-80T>C	intron_variant	Intron 1 of 4			ENSP00000502615.1	P11226
MBL2	ENST00000373968.3 link	c.-104T>C	upstream_gene_variant		1		ENSP00000363079.3	P11226

Frequencies

GnomAD3 genomes

AF:

0.000775

AC:

118

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00628

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00478

GnomAD4 exome

AF:

0.000190

AC:

249

AN:

1310100

Hom.:

Cov.:

AF XY:

0.000163

AC XY:

104

AN XY:

636826

show subpopulations

African (AFR)

AF:

0.000139

AC:

AN:

28860

American (AMR)

AF:

0.00711

AC:

177

AN:

24902

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19512

East Asian (EAS)

AF:

0.00

AC:

AN:

34988

South Asian (SAS)

AF:

0.00

AC:

AN:

65092

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44310

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4130

European-Non Finnish (NFE)

AF:

0.0000300

AC:

AN:

1034242

Other (OTH)

AF:

0.000684

AC:

AN:

54064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000775

AC:

118

AN:

152300

Hom.:

Cov.:

AF XY:

0.000779

AC XY:

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41562

American (AMR)

AF:

0.00628

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68024

Other (OTH)

AF:

0.00473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000416

Hom.:

Bravo

AF:

0.00149

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.3

(source)

DANN

Benign

0.55

PhyloP100

-0.76

PromoterAI

0.065

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over