chr2-118981487-T-G

Variant names:

• chr2-118981487-T-G
• rs6761637
• NM_006770.4:c.845T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006770.4(MARCO):​c.845T>G​(p.Phe282Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MARCO NM_006770.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288
• Publications: 22 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26104432).

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.845T>G	p.Phe282Cys	missense	Exon 9 of 17	NP_006761.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCO	ENST00000327097.5	TSL:1 MANE Select	c.845T>G	p.Phe282Cys	missense	Exon 9 of 17	ENSP00000318916.4
	MARCO	ENST00000874357.1		c.845T>G	p.Phe282Cys	missense	Exon 9 of 18	ENSP00000544416.1
	MARCO	ENST00000958830.1		c.845T>G	p.Phe282Cys	missense	Exon 9 of 17	ENSP00000628889.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Benign	0.42
DEOGEN2	Benign	0.081	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	-0.084	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.29
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.61	N
REVEL	Benign	0.13
Sift	Benign	0.18	T
Sift4G	Benign	0.11	T
Polyphen		0.0040	B
Vest4		0.12
MutPred		0.19		Gain of glycosylation at S278 (P = 0.1201)
MVP		0.69
MPC		0.064
ClinPred		0.097	T
GERP RS		4.5
Varity_R		0.050
gMVP		0.30
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs6761637; hg19: chr2-119739063;