rs691773

chr10-17862853-A-Gchr10-17862853-A-T

Variant summary

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

The NM_002438.4(MRC1):c.1635-681A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,164 control chromosomes in the GnomAD database, including 60,260 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 0.89 (60255 hom., cov: 32)
  • Exomes 𝑓: 0.81 (5 hom.)
• Consequence: MRC1 NM_002438.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.693

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRC1	NM_002438.4	c.1635-681A>G		intron_variant		ENST00000569591.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRC1	ENST00000569591.3	c.1635-681A>G		intron_variant		1	NM_002438.4	P1
	ENST00000442231.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135255 AN: 152030 Hom.: 60191 Cov.: 32

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.971

Gnomad AMR AF: 0.894

Gnomad ASJ AF: 0.944

Gnomad EAS AF: 0.861

Gnomad SAS AF: 0.926

Gnomad FIN AF: 0.878

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.903

Gnomad OTH AF: 0.889

GnomAD4 exome AF: 0.813 AC: 13 AN: 16 Hom.: 5 Cov.: 0 AF XY: 0.750 AC XY: 9 AN XY: 12

Gnomad4 AMR exome AF: 1.00

Gnomad4 NFE exome AF: 0.786

GnomAD4 genome AF: 0.890 AC: 135376 AN: 152148 Hom.: 60255 Cov.: 32 AF XY: 0.889 AC XY: 66130 AN XY: 74372

Gnomad4 AFR AF: 0.862

Gnomad4 AMR AF: 0.894

Gnomad4 ASJ AF: 0.944

Gnomad4 EAS AF: 0.862

Gnomad4 SAS AF: 0.927

Gnomad4 FIN AF: 0.878

Gnomad4 NFE AF: 0.903

Gnomad4 OTH AF: 0.889

Alfa AF: 0.897 Hom.: 5184

Bravo AF: 0.889

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.35
Dann	Benign	0.72

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

Other links and lift over

dbSNP: rs691773; hg19: chr10-18151782;