chr10-17870917-T-C

Variant names:

• chr10-17870917-T-C
• rs1443502
• NM_002438.4:c.2181T>C

Variant summary

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

The NM_002438.4(MRC1):​c.2181T>C​(p.Thr727Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 872,024 control chromosomes in the GnomAD database, including 28,419 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 0.22 (4247 hom., cov: 32)
  • Exomes 𝑓: 0.24 (24172 hom.)
• Consequence: MRC1 NM_002438.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 2 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 (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.294 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRC1	NM_002438.4	MANE Select	c.2181T>C	p.Thr727Thr	synonymous	Exon 14 of 30	NP_002429.1	P22897-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRC1	ENST00000569591.3	TSL:1 MANE Select	c.2181T>C	p.Thr727Thr	synonymous	Exon 14 of 30	ENSP00000455897.1	P22897-1
	MRC1	ENST00000954013.1		c.2067T>C	p.Thr689Thr	synonymous	Exon 13 of 29	ENSP00000624072.1
	MRC1	ENST00000884128.1		c.2007T>C	p.Thr669Thr	synonymous	Exon 13 of 29	ENSP00000554187.1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33281 AN: 152060 Hom.: 4247 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.00481

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.203

GnomAD4 exome AF: 0.241 AC: 173600 AN: 719846 Hom.: 24172 Cov.: 0 AF XY: 0.238 AC XY: 91424 AN XY: 384308

African (AFR) AF: 0.128 AC: 2537 AN: 19848

American (AMR) AF: 0.119 AC: 5230 AN: 43876

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 3978 AN: 21480

East Asian (EAS) AF: 0.00214 AC: 78 AN: 36492

South Asian (SAS) AF: 0.121 AC: 8644 AN: 71702

European-Finnish (FIN) AF: 0.300 AC: 15966 AN: 53166

Middle Eastern (MID) AF: 0.202 AC: 871 AN: 4308

European-Non Finnish (NFE) AF: 0.296 AC: 128104 AN: 432976

Other (OTH) AF: 0.228 AC: 8192 AN: 35998

GnomAD4 genome AF: 0.219 AC: 33291 AN: 152178 Hom.: 4247 Cov.: 32 AF XY: 0.216 AC XY: 16063 AN XY: 74406

African (AFR) AF: 0.129 AC: 5378 AN: 41536

American (AMR) AF: 0.165 AC: 2524 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 597 AN: 3470

East Asian (EAS) AF: 0.00482 AC: 25 AN: 5188

South Asian (SAS) AF: 0.115 AC: 554 AN: 4828

European-Finnish (FIN) AF: 0.297 AC: 3146 AN: 10576

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20221 AN: 67970

Other (OTH) AF: 0.200 AC: 422 AN: 2114

Alfa AF: 0.245 Hom.: 476

Bravo AF: 0.205

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.0
DANN	Benign	0.73
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism

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: rs1443502; hg19: chr10-18159846;