rs2985837

Positions:

• chr10-17833763-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002438.4(MRC1):​c.726G>A​(p.Gln242Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 780,816 control chromosomes in the GnomAD database, including 52,106 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 0.37 (10811 hom., cov: 32)
  • Exomes 𝑓: 0.36 (41295 hom.)
• Consequence: MRC1 NM_002438.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=1.51 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRC1	NM_002438.4	c.726G>A	p.Gln242Gln	synonymous_variant	4/30	ENST00000569591.3	NP_002429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRC1	ENST00000569591.3	c.726G>A	p.Gln242Gln	synonymous_variant	4/30	1	NM_002438.4	ENSP00000455897.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56837 AN: 151920 Hom.: 10804 Cov.: 32

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.386

GnomAD3 exomes AF: 0.00373 AC: 785 AN: 210484 Hom.: 149 AF XY: 0.00354 AC XY: 406 AN XY: 114688

Gnomad AFR exome AF: 0.00411

Gnomad AMR exome AF: 0.00712

Gnomad ASJ exome AF: 0.00453

Gnomad EAS exome AF: 0.00581

Gnomad SAS exome AF: 0.00182

Gnomad FIN exome AF: 0.000156

Gnomad NFE exome AF: 0.00350

Gnomad OTH exome AF: 0.00373

GnomAD4 exome AF: 0.358 AC: 225364 AN: 628778 Hom.: 41295 Cov.: 0 AF XY: 0.354 AC XY: 121350 AN XY: 342530

Gnomad4 AFR exome AF: 0.401

Gnomad4 AMR exome AF: 0.366

Gnomad4 ASJ exome AF: 0.379

Gnomad4 EAS exome AF: 0.298

Gnomad4 SAS exome AF: 0.277

Gnomad4 FIN exome AF: 0.339

Gnomad4 NFE exome AF: 0.380

Gnomad4 OTH exome AF: 0.359

GnomAD4 genome AF: 0.374 AC: 56882 AN: 152038 Hom.: 10811 Cov.: 32 AF XY: 0.372 AC XY: 27639 AN XY: 74318

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.386

Alfa AF: 0.377 Hom.: 1047

Bravo AF: 0.375

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	4.7
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2985837; hg19: chr10-17875762; COSMIC: COSV58889040;