rs2947600

Variant names:

• chr10-17817451-T-C
• rs2947600
• NM_002438.4:c.62-5623T>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.62-5623T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 151,968 control chromosomes in the GnomAD database, including 43,062 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 0.74 (43062 hom., cov: 30)
• Consequence: MRC1 NM_002438.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.686
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRC1	NM_002438.4	c.62-5623T>C		intron_variant	Intron 1 of 29	ENST00000569591.3	NP_002429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRC1	ENST00000569591.3	c.62-5623T>C		intron_variant	Intron 1 of 29	1	NM_002438.4	ENSP00000455897.1

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112726 AN: 151850 Hom.: 43015 Cov.: 30

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.735

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.742 AC: 112836 AN: 151968 Hom.: 43062 Cov.: 30 AF XY: 0.738 AC XY: 54828 AN XY: 74278

African (AFR) AF: 0.928 AC: 38462 AN: 41444

American (AMR) AF: 0.637 AC: 9718 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 2432 AN: 3464

East Asian (EAS) AF: 0.625 AC: 3226 AN: 5162

South Asian (SAS) AF: 0.689 AC: 3319 AN: 4818

European-Finnish (FIN) AF: 0.628 AC: 6611 AN: 10534

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.687 AC: 46682 AN: 67970

Other (OTH) AF: 0.733 AC: 1550 AN: 2114

Alfa AF: 0.734 Hom.: 3851

Bravo AF: 0.750

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.5
DANN	Benign	0.49
PhyloP100		-0.69
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: rs2947600; hg19: chr10-17859450;