2-118942009-C-G

Variant names:

• chr2-118942009-C-G
• rs1318645
• NM_006770.4:c.-292C>G

Variant summary

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

The NM_006770.4(MARCO):​c.-292C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,834 control chromosomes in the GnomAD database, including 28,996 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 0.62 (28996 hom., cov: 30)
• Consequence: MARCO NM_006770.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880
• Publications: 9 publications found

Genes affected

MARCO (HGNC:6895): (macrophage receptor with collagenous structure) The protein encoded by this gene is a member of the class A scavenger receptor family and is part of the innate antimicrobial immune system. The protein may bind both Gram-negative and Gram-positive bacteria via an extracellular, C-terminal, scavenger receptor cysteine-rich (SRCR) domain. In addition to short cytoplasmic and transmembrane domains, there is an extracellular spacer domain and a long, extracellular collagenous domain. The protein may form a trimeric molecule by the association of the collagenous domains of three identical polypeptide chains. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006770.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCO	NM_006770.4	MANE Select	c.-292C>G		upstream_gene	N/A	NP_006761.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCO	ENST00000327097.5	TSL:1 MANE Select	c.-292C>G		upstream_gene	N/A	ENSP00000318916.4
	MARCO	ENST00000874357.1		c.-292C>G		upstream_gene	N/A	ENSP00000544416.1
	MARCO	ENST00000958830.1		c.-292C>G		upstream_gene	N/A	ENSP00000628889.1

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93420 AN: 151716 Hom.: 28980 Cov.: 30

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.616 AC: 93479 AN: 151834 Hom.: 28996 Cov.: 30 AF XY: 0.610 AC XY: 45237 AN XY: 74186

African (AFR) AF: 0.594 AC: 24588 AN: 41390

American (AMR) AF: 0.637 AC: 9719 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2437 AN: 3468

East Asian (EAS) AF: 0.638 AC: 3267 AN: 5118

South Asian (SAS) AF: 0.423 AC: 2037 AN: 4810

European-Finnish (FIN) AF: 0.569 AC: 5995 AN: 10534

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.639 AC: 43428 AN: 67930

Other (OTH) AF: 0.632 AC: 1336 AN: 2114

Alfa AF: 0.490 Hom.: 1260

Bravo AF: 0.627

Asia WGS AF: 0.508 AC: 1765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.46
PhyloP100		-0.088
PromoterAI		0.014	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1318645; hg19: chr2-119699585;