rs7095891

Variant names:

• chr10-52771701-G-A
• rs7095891
• NM_001378373.1:c.-9-57C>T

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.-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
• Publications: 92 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 10-52771701-G-A is Benign according to our data. Variant chr10-52771701-G-A is described in ClinVar as Likely_benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
MBL2	NM_001378373.1	c.-9-57C>T		intron_variant	Intron 1 of 4	ENST00000674931.1	NP_001365302.1
MBL2	NM_001378374.1	c.-24-42C>T		intron_variant	Intron 1 of 4		NP_001365303.1
MBL2	NM_000242.3	c.-66C>T		upstream_gene_variant			NP_000233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBL2	ENST00000674931.1	c.-9-57C>T		intron_variant	Intron 1 of 4		NM_001378373.1	ENSP00000502789.1
MBL2	ENST00000675947.1	c.-24-42C>T		intron_variant	Intron 1 of 4			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

African (AFR) AF: 0.522 AC: 16444 AN: 31508

American (AMR) AF: 0.167 AC: 5990 AN: 35962

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 6027 AN: 22936

East Asian (EAS) AF: 0.138 AC: 5035 AN: 36374

South Asian (SAS) AF: 0.241 AC: 18075 AN: 75098

European-Finnish (FIN) AF: 0.174 AC: 8570 AN: 49302

Middle Eastern (MID) AF: 0.221 AC: 1160 AN: 5248

European-Non Finnish (NFE) AF: 0.225 AC: 240698 AN: 1069686

Other (OTH) AF: 0.231 AC: 13228 AN: 57280

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

African (AFR) AF: 0.508 AC: 21051 AN: 41478

American (AMR) AF: 0.215 AC: 3284 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 909 AN: 3460

East Asian (EAS) AF: 0.137 AC: 706 AN: 5168

South Asian (SAS) AF: 0.245 AC: 1181 AN: 4820

European-Finnish (FIN) AF: 0.174 AC: 1846 AN: 10580

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14756 AN: 67996

Other (OTH) AF: 0.267 AC: 563 AN: 2112

Alfa AF: 0.300 Hom.: 3591

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mannose-binding lectin deficiency Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.45
PhyloP100		-0.51
PromoterAI		-0.0020	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

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