rs374405181

Variant names:

• chr2-118969204-G-A
• rs374405181
• NM_006770.4:c.142G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-118969204-G-A
• chr2-118969204-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006770.4(MARCO):​c.142G>A​(p.Val48Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000261 in 1,614,102 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00027 (1 hom.)
• Consequence: MARCO NM_006770.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.04
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.030349433).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCO	NM_006770.4	MANE Select	c.142G>A	p.Val48Met	missense	Exon 2 of 17	NP_006761.1	Q4ZG40

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCO	ENST00000327097.5	TSL:1 MANE Select	c.142G>A	p.Val48Met	missense	Exon 2 of 17	ENSP00000318916.4	Q9UEW3-1
	MARCO	ENST00000412481.1	TSL:4	c.-93G>A		5_prime_UTR_premature_start_codon_gain	Exon 3 of 4	ENSP00000409192.1	C9JKT8
	MARCO	ENST00000874357.1		c.142G>A	p.Val48Met	missense	Exon 2 of 18	ENSP00000544416.1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152234 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000147 AC: 37 AN: 251426 AF XY: 0.000125

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.000496

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000211

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000275 AC: 402 AN: 1461868 Hom.: 1 Cov.: 30 AF XY: 0.000278 AC XY: 202 AN XY: 727242

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.000157 AC: 7 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000344 AC: 9 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000334 AC: 371 AN: 1111988

Other (OTH) AF: 0.000215 AC: 13 AN: 60396

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152234 Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10 AN XY: 74368

African (AFR) AF: 0.0000965 AC: 4 AN: 41460

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000213 Hom.: 0

Bravo AF: 0.000132

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000107 AC: 13

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.0030
DANN	Benign	0.41
DEOGEN2	Benign	0.086	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0045	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	0.55	N
PhyloP100		-3.0
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.21
Sift	Benign	0.24	T
Sift4G	Benign	0.21	T
Polyphen		0.0050	B
Vest4		0.18
MVP		0.23
MPC		0.092
ClinPred		0.050	T
GERP RS		-10
Varity_R		0.021
gMVP		0.43
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs374405181; hg19: chr2-119726780; COSMIC: COSV59057927;