2-118942395-A-G

Position:

chr2-118942395-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_006770.4(MARCO):c.95A>G(p.Asn32Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000385 in 1,609,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

MARCO
NM_006770.4 missense, splice_region

Scores

Splicing: ADA: 0.0003354

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.155

Variant links:

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]

MARCO links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.025675863).

BP6

Variant 2-118942395-A-G is Benign according to our data. Variant chr2-118942395-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2217547.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MARCO	NM_006770.4 linkuse as main transcript	c.95A>G	p.Asn32Ser	missense_variant, splice_region_variant	1/17	ENST00000327097.5	NP_006761.1
MARCO	XM_011512082.3 linkuse as main transcript	c.95A>G	p.Asn32Ser	missense_variant, splice_region_variant	1/17		XP_011510384.1
MARCO	XM_011512083.4 linkuse as main transcript	c.95A>G	p.Asn32Ser	missense_variant, splice_region_variant	1/14		XP_011510385.1
MARCO	XM_017005171.3 linkuse as main transcript	c.95A>G	p.Asn32Ser	missense_variant, splice_region_variant	1/9		XP_016860660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARCO	ENST00000327097.5 linkuse as main transcript	c.95A>G	p.Asn32Ser	missense_variant, splice_region_variant	1/17	1	NM_006770.4	ENSP00000318916	P1	Q9UEW3-1
MARCO	ENST00000412481.1 linkuse as main transcript	c.-273A>G		splice_region_variant, 5_prime_UTR_variant	1/4	4		ENSP00000409192

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

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:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000399

AC:

AN:

250420

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135390

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000443

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.0000261

AC:

AN:

1456856

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

725066

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000993

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000158

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000317

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.54

CADD

Benign

3.2

DANN

Benign

0.20

DEOGEN2

Benign

0.069

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.54

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.026

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.60

REVEL

Benign

0.23

Sift

Benign

0.91

Sift4G

Benign

0.65

Polyphen

0.0

Vest4

0.11

MutPred

0.27

Gain of glycosylation at N32 (P = 0.0521);

MVP

0.22

MPC

0.042

ClinPred

0.029

GERP RS

-3.0

Varity_R

0.030

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00034

dbscSNV1_RF

Benign

0.046

SpliceAI score (max)

0.18

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over