10-17849710-A-G

Variant names:

• chr10-17849710-A-G
• rs71497223
• NM_002438.4:c.1195A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.82 (51028 hom., cov: 30)
  • Exomes 𝑓: 0.83 (217338 hom.)
• Consequence: MRC1 NM_002438.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.38
• Publications: 10 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002438.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRC1	NM_002438.4	MANE Select	c.1195A>G	p.Thr399Ala	missense	Exon 7 of 30	NP_002429.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRC1	ENST00000569591.3	TSL:1 MANE Select	c.1195A>G	p.Thr399Ala	missense	Exon 7 of 30	ENSP00000455897.1

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124141 AN: 151726 Hom.: 50985 Cov.: 30

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

GnomAD2 exomes AF: 0.0559 AC: 4203 AN: 75130 AF XY: 0.0453

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 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.: 0 AF XY: 0.829 AC XY: 284102 AN XY: 342510

African (AFR) AF: 0.825 AC: 14587 AN: 17688

American (AMR) AF: 0.877 AC: 38377 AN: 43738

Ashkenazi Jewish (ASJ) AF: 0.830 AC: 17404 AN: 20980

East Asian (EAS) AF: 0.999 AC: 36029 AN: 36064

South Asian (SAS) AF: 0.873 AC: 60963 AN: 69796

European-Finnish (FIN) AF: 0.873 AC: 46407 AN: 53144

Middle Eastern (MID) AF: 0.813 AC: 3374 AN: 4148

European-Non Finnish (NFE) AF: 0.791 AC: 276884 AN: 350068

Other (OTH) AF: 0.821 AC: 27161 AN: 33098

GnomAD4 genome AF: 0.818 AC: 124242 AN: 151844 Hom.: 51028 Cov.: 30 AF XY: 0.825 AC XY: 61191 AN XY: 74204

African (AFR) AF: 0.823 AC: 34086 AN: 41408

American (AMR) AF: 0.827 AC: 12595 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.834 AC: 2886 AN: 3462

East Asian (EAS) AF: 0.998 AC: 5144 AN: 5156

South Asian (SAS) AF: 0.884 AC: 4250 AN: 4806

European-Finnish (FIN) AF: 0.871 AC: 9173 AN: 10532

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.787 AC: 53479 AN: 67934

Other (OTH) AF: 0.816 AC: 1719 AN: 2106

Alfa AF: 0.793 Hom.: 5628

Bravo AF: 0.815

ExAC AF: 0.118 AC: 6021

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.7
DANN	Benign	0.52
DEOGEN2	Benign	0.059	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.061	T
MetaRNN	Benign	0.0000021	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-2.2	N
PhyloP100		4.4
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	2.1	N
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.046
ClinPred		0.0037	T
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

Other links and lift over

dbSNP: rs71497223; hg19: chr10-18138639;