rs67990116

Positions:

• chr10-52771815-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001378373.1(MBL2):​c.-9-171A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 898,218 control chromosomes in the GnomAD database, including 16 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 0.0061 (10 hom., cov: 33)
  • Exomes 𝑓: 0.00059 (6 hom.)
• Consequence: MBL2 NM_001378373.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.774

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00609 (928/152326) while in subpopulation AFR AF= 0.0211 (878/41574). AF 95% confidence interval is 0.02. There are 10 homozygotes in gnomad4. There are 418 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 928 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBL2	NM_001378373.1	c.-9-171A>T		intron_variant		ENST00000674931.1	NP_001365302.1
MBL2	NM_001378374.1	c.-24-156A>T		intron_variant			NP_001365303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBL2	ENST00000674931.1	c.-9-171A>T		intron_variant			NM_001378373.1	ENSP00000502789	P1
MBL2	ENST00000675947.1	c.-24-156A>T		intron_variant				ENSP00000502615	P1

Frequencies

GnomAD3 genomes AF: 0.00608 AC: 926 AN: 152208 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.0211

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

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: 0.000132

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.000586 AC: 437 AN: 745892 Hom.: 6 AF XY: 0.000506 AC XY: 190 AN XY: 375254

Gnomad4 AFR exome AF: 0.0197

Gnomad4 AMR exome AF: 0.00142

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000191

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000419

Gnomad4 OTH exome AF: 0.00100

GnomAD4 genome AF: 0.00609 AC: 928 AN: 152326 Hom.: 10 Cov.: 33 AF XY: 0.00561 AC XY: 418 AN XY: 74502

Gnomad4 AFR AF: 0.0211

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00140 Hom.: 0

Bravo AF: 0.00692

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.49
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs67990116; hg19: chr10-54531575;