Variant 10-17849701-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002438.4(MRC1):c.1186G>A(p.Gly396Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.381 in 780,628 control chromosomes in the GnomAD database, including 60,175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain risk allele,risk factor (no stars).

Frequency

Genomes: 𝑓 0.32 ( 9039 hom., cov: 31)

Exomes 𝑓: 0.40 ( 51136 hom. )

Consequence

MRC1
NM_002438.4 missense

Scores

Clinical Significance

Uncertain risk allele; risk factor no assertion criteria provided O:2

Conservation

PhyloP100: 8.17

Variant links:

Genes affected

MRC1 (HGNC:7228): (mannose receptor C-type 1) The recognition of complex carbohydrate structures on glycoproteins is an important part of several biological processes, including cell-cell recognition, serum glycoprotein turnover, and neutralization of pathogens. The protein encoded by this gene is a type I membrane receptor that mediates the endocytosis of glycoproteins by macrophages. The protein has been shown to bind high-mannose structures on the surface of potentially pathogenic viruses, bacteria, and fungi so that they can be neutralized by phagocytic engulfment.[provided by RefSeq, Sep 2015]

MRC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01415357).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRC1	NM_002438.4 linkuse as main transcript	c.1186G>A	p.Gly396Ser	missense_variant	7/30	ENST00000569591.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRC1	ENST00000569591.3 linkuse as main transcript	c.1186G>A	p.Gly396Ser	missense_variant	7/30	1	NM_002438.4	P1	P22897-1

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48827

AN:

151802

Hom.:

9043

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.370

Gnomad AMR

AF:

0.426

Gnomad ASJ

AF:

0.363

Gnomad EAS

AF:

0.458

Gnomad SAS

AF:

0.422

Gnomad FIN

AF:

0.472

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.372

Gnomad OTH

AF:

0.331

GnomAD3 exomes

AF:

0.0000129

AC:

AN:

77524

Hom.:

AF XY:

0.00

AC XY:

AN XY:

42018

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.396

AC:

248770

AN:

628708

Hom.:

51136

Cov.:

AF XY:

0.396

AC XY:

135720

AN XY:

342502

show subpopulations

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.496

Gnomad4 ASJ exome

AF:

0.365

Gnomad4 EAS exome

AF:

0.466

Gnomad4 SAS exome

AF:

0.428

Gnomad4 FIN exome

AF:

0.468

Gnomad4 NFE exome

AF:

0.377

Gnomad4 OTH exome

AF:

0.369

GnomAD4 genome

AF:

0.321

AC:

48832

AN:

151920

Hom.:

9039

Cov.:

AF XY:

0.329

AC XY:

24456

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.128

Gnomad4 AMR

AF:

0.426

Gnomad4 ASJ

AF:

0.363

Gnomad4 EAS

AF:

0.458

Gnomad4 SAS

AF:

0.423

Gnomad4 FIN

AF:

0.472

Gnomad4 NFE

AF:

0.372

Gnomad4 OTH

AF:

0.330

Alfa

AF:

0.323

Hom.:

797

Bravo

AF:

0.310

ExAC

AF:

0.0000187

AC:

ClinVar

Significance: Uncertain risk allele; risk factor

Submissions summary: Other:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Leprosy, susceptibility to, 1

Other:1

Uncertain risk allele, no assertion criteria provided

case-control

Centro Dermatológico Federico Lleras Acosta, Hospital Universitario Centro Dermatológico Federico Lleras Acosta

Jun 10, 2022

- -

Susceptibility to leprosy and multibacillary leprosy

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 01, 2010

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

M_CAP

Benign

0.050

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.5

Sift

Benign

0.16

Sift4G

Benign

0.14

Polyphen

1.0

Vest4

0.55

MVP

0.43

ClinPred

0.93

GERP RS

4.3

Varity_R

0.61

gMVP

0.80

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over