Variant rs71497223 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.1195A>G(p.Thr399Ala) variant causes a missense change. The variant allele was found at a frequency of 0.827 in 780,568 control chromosomes in the GnomAD database, including 268,366 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.82 ( 51028 hom., cov: 30)

Exomes 𝑓: 0.83 ( 217338 hom. )

Consequence

MRC1
NM_002438.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.38

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=2.1414721E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRC1	NM_002438.4 linkuse as main transcript	c.1195A>G	p.Thr399Ala	missense_variant	7/30	ENST00000569591.3	NP_002429.1	P22897-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRC1	ENST00000569591.3 linkuse as main transcript	c.1195A>G	p.Thr399Ala	missense_variant	7/30	1	NM_002438.4	ENSP00000455897.1		P22897-1

Frequencies

GnomAD3 genomes

AF:

0.818

AC:

124141

AN:

151726

Hom.:

50985

Cov.:

show subpopulations

Gnomad AFR

AF:

0.823

Gnomad AMI

AF:

0.733

Gnomad AMR

AF:

0.826

Gnomad ASJ

AF:

0.834

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.884

Gnomad FIN

AF:

0.871

Gnomad MID

AF:

0.835

Gnomad NFE

AF:

0.787

Gnomad OTH

AF:

0.816

GnomAD3 exomes

AF:

0.0559

AC:

4203

AN:

75130

Hom.:

2030

AF XY:

0.0453

AC XY:

1851

AN XY:

40822

show subpopulations

Gnomad AFR exome

AF:

0.291

Gnomad AMR exome

AF:

0.0131

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.962

Gnomad SAS exome

AF:

0.0252

Gnomad FIN exome

AF:

0.000798

Gnomad NFE exome

AF:

0.00185

Gnomad OTH exome

AF:

0.0168

GnomAD4 exome

AF:

0.829

AC:

521186

AN:

628724

Hom.:

217338

Cov.:

AF XY:

0.829

AC XY:

284102

AN XY:

342510

show subpopulations

Gnomad4 AFR exome

AF:

0.825

Gnomad4 AMR exome

AF:

0.877

Gnomad4 ASJ exome

AF:

0.830

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.873

Gnomad4 FIN exome

AF:

0.873

Gnomad4 NFE exome

AF:

0.791

Gnomad4 OTH exome

AF:

0.821

GnomAD4 genome

AF:

0.818

AC:

124242

AN:

151844

Hom.:

51028

Cov.:

AF XY:

0.825

AC XY:

61191

AN XY:

74204

show subpopulations

Gnomad4 AFR

AF:

0.823

Gnomad4 AMR

AF:

0.827

Gnomad4 ASJ

AF:

0.834

Gnomad4 EAS

AF:

0.998

Gnomad4 SAS

AF:

0.884

Gnomad4 FIN

AF:

0.871

Gnomad4 NFE

AF:

0.787

Gnomad4 OTH

AF:

0.816

Alfa

AF:

0.666

Hom.:

810

Bravo

AF:

0.815

ExAC

AF:

0.118

AC:

6021

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

6.7

DANN

Benign

0.52

DEOGEN2

Benign

0.059

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.061

MetaRNN

Benign

0.0000021

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-2.2

PrimateAI

Uncertain

0.58

PROVEAN

Benign

2.1

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.046

ClinPred

0.0037

GERP RS

3.5

Varity_R

0.17

gMVP

0.39

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over