rs6761637

Positions:

• chr2-118981487-T-C
• chr2-118981487-T-G

Variant summary

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

The NM_006770.4(MARCO):​c.845T>C​(p.Phe282Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0685 in 1,599,326 control chromosomes in the GnomAD database, including 6,786 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.13 (2148 hom., cov: 32)
  • Exomes 𝑓: 0.063 (4638 hom.)
• Consequence: MARCO NM_006770.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0289945).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARCO	NM_006770.4	c.845T>C	p.Phe282Ser	missense_variant	9/17	ENST00000327097.5	NP_006761.1
MARCO	XM_011512082.3	c.845T>C	p.Phe282Ser	missense_variant	9/17		XP_011510384.1
MARCO	XM_011512083.4	c.482T>C	p.Phe161Ser	missense_variant	6/14		XP_011510385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARCO	ENST00000327097.5	c.845T>C	p.Phe282Ser	missense_variant	9/17	1	NM_006770.4	ENSP00000318916	P1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18868 AN: 150962 Hom.: 2138 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0625

Gnomad ASJ AF: 0.0759

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0213

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.0514

Gnomad OTH AF: 0.114

GnomAD3 exomes AF: 0.0832 AC: 19804 AN: 238090 Hom.: 1512 AF XY: 0.0829 AC XY: 10687 AN XY: 128976

Gnomad AFR exome AF: 0.310

Gnomad AMR exome AF: 0.0388

Gnomad ASJ exome AF: 0.0702

Gnomad EAS exome AF: 0.122

Gnomad SAS exome AF: 0.160

Gnomad FIN exome AF: 0.0255

Gnomad NFE exome AF: 0.0505

Gnomad OTH exome AF: 0.0672

GnomAD4 exome AF: 0.0626 AC: 90630 AN: 1448308 Hom.: 4638 Cov.: 31 AF XY: 0.0651 AC XY: 46941 AN XY: 720542

Gnomad4 AFR exome AF: 0.311

Gnomad4 AMR exome AF: 0.0416

Gnomad4 ASJ exome AF: 0.0716

Gnomad4 EAS exome AF: 0.0856

Gnomad4 SAS exome AF: 0.161

Gnomad4 FIN exome AF: 0.0242

Gnomad4 NFE exome AF: 0.0489

Gnomad4 OTH exome AF: 0.0725

GnomAD4 genome AF: 0.125 AC: 18907 AN: 151018 Hom.: 2148 Cov.: 32 AF XY: 0.124 AC XY: 9145 AN XY: 73604

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.0624

Gnomad4 ASJ AF: 0.0759

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.0213

Gnomad4 NFE AF: 0.0514

Gnomad4 OTH AF: 0.117

Alfa AF: 0.0834 Hom.: 558

Bravo AF: 0.133

TwinsUK AF: 0.0461 AC: 171

ALSPAC AF: 0.0428 AC: 165

ESP6500AA AF: 0.295 AC: 1300

ESP6500EA AF: 0.0521 AC: 448

ExAC AF: 0.0897 AC: 10892

Asia WGS AF: 0.109 AC: 381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.8
DANN	Benign	0.83
DEOGEN2	Benign	0.043	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.00036	N
LIST_S2	Benign	0.14	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.59	N
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	3.5	N
REVEL	Benign	0.20
Sift	Benign	0.70	T
Sift4G	Benign	0.88	T
Polyphen		0.0	B
Vest4		0.028
MPC		0.076
ClinPred		0.0011	T
GERP RS		4.5
Varity_R		0.039
gMVP		0.17

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: rs6761637; hg19: chr2-119739063; COSMIC: COSV59055097;