10-17827578-C-T

Variant names:

• chr10-17827578-C-T
• rs2296414
• NM_002438.4:c.500C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002438.4(MRC1):​c.500C>T​(p.Thr167Ile) variant causes a missense change. The variant allele was found at a frequency of 0.188 in 780,570 control chromosomes in the GnomAD database, including 15,337 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/16 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.16 (2452 hom., cov: 31)
  • Exomes 𝑓: 0.19 (12885 hom.)
• Consequence: MRC1 NM_002438.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.95

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.035351604).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRC1	NM_002438.4	c.500C>T	p.Thr167Ile	missense_variant	Exon 3 of 30	ENST00000569591.3	NP_002429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRC1	ENST00000569591.3	c.500C>T	p.Thr167Ile	missense_variant	Exon 3 of 30	1	NM_002438.4	ENSP00000455897.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24620 AN: 151898 Hom.: 2448 Cov.: 31

Gnomad AFR AF: 0.0495

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.168

GnomAD3 exomes AF: 0.240 AC: 4530 AN: 18860 Hom.: 779 AF XY: 0.239 AC XY: 2322 AN XY: 9734

Gnomad AFR exome AF: 0.0626

Gnomad AMR exome AF: 0.111

Gnomad ASJ exome AF: 0.308

Gnomad EAS exome AF: 0.302

Gnomad SAS exome AF: 0.130

Gnomad FIN exome AF: 0.283

Gnomad NFE exome AF: 0.309

Gnomad OTH exome AF: 0.247

GnomAD4 exome AF: 0.195 AC: 122273 AN: 628556 Hom.: 12885 Cov.: 0 AF XY: 0.194 AC XY: 66360 AN XY: 342426

Gnomad4 AFR exome AF: 0.0517

Gnomad4 AMR exome AF: 0.101

Gnomad4 ASJ exome AF: 0.230

Gnomad4 EAS exome AF: 0.233

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.222

Gnomad4 NFE exome AF: 0.215

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.162 AC: 24620 AN: 152014 Hom.: 2452 Cov.: 31 AF XY: 0.161 AC XY: 12000 AN XY: 74310

Gnomad4 AFR AF: 0.0494

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.171

Alfa AF: 0.210 Hom.: 2038

Bravo AF: 0.153

ExAC AF: 0.122 AC: 1354

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	16
DANN	Benign	0.81
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.6	N
Sift	Benign	0.15	T
Sift4G	Uncertain	0.015	D
Vest4		0.020
ClinPred		0.016	T
GERP RS		3.1
Varity_R		0.080
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs2296414; hg19: chr10-17869577; COSMIC: COSV58889077;