Genetic Variant MARCO:c.97+123T>C (chr2-118942520-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006770.4(MARCO):c.97+123T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 711,290 control chromosomes in the GnomAD database, including 137,373 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 ( 29058 hom., cov: 33)

Exomes 𝑓: 0.62 ( 108315 hom. )

Consequence

MARCO
NM_006770.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.698

Publications

4 publications found

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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
MARCO	NM_006770.4 link	c.97+123T>C	intron_variant	Intron 1 of 16	ENST00000327097.5	NP_006761.1
MARCO	XM_011512082.3 link	c.97+123T>C	intron_variant	Intron 1 of 16		XP_011510384.1
MARCO	XM_011512083.4 link	c.97+123T>C	intron_variant	Intron 1 of 13		XP_011510385.1
MARCO	XM_017005171.3 link	c.97+123T>C	intron_variant	Intron 1 of 8		XP_016860660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARCO	ENST00000327097.5 link	c.97+123T>C		intron_variant	Intron 1 of 16	1	NM_006770.4	ENSP00000318916.4
MARCO	ENST00000412481.1 link	c.-271+123T>C		intron_variant	Intron 1 of 3	4		ENSP00000409192.1

Frequencies

GnomAD3 genomes

AF:

0.616

AC:

93599

AN:

151982

Hom.:

29042

Cov.:

show subpopulations

Gnomad AFR

AF:

0.594

Gnomad AMI

AF:

0.523

Gnomad AMR

AF:

0.638

Gnomad ASJ

AF:

0.703

Gnomad EAS

AF:

0.638

Gnomad SAS

AF:

0.426

Gnomad FIN

AF:

0.569

Gnomad MID

AF:

0.650

Gnomad NFE

AF:

0.639

Gnomad OTH

AF:

0.633

GnomAD4 exome

AF:

0.616

AC:

344508

AN:

559190

Hom.:

108315

AF XY:

0.606

AC XY:

178920

AN XY:

295254

show subpopulations

African (AFR)

AF:

0.600

AC:

8892

AN:

14818

American (AMR)

AF:

0.636

AC:

17688

AN:

27816

Ashkenazi Jewish (ASJ)

AF:

0.706

AC:

11444

AN:

16212

East Asian (EAS)

AF:

0.631

AC:

19674

AN:

31168

South Asian (SAS)

AF:

0.413

AC:

22043

AN:

53412

European-Finnish (FIN)

AF:

0.583

AC:

22585

AN:

38718

Middle Eastern (MID)

AF:

0.614

AC:

2261

AN:

3682

European-Non Finnish (NFE)

AF:

0.644

AC:

221225

AN:

343704

Other (OTH)

AF:

0.630

AC:

18696

AN:

29660

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

6167

12334

18501

24668

30835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2220

4440

6660

8880

11100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.616

AC:

93658

AN:

152100

Hom.:

29058

Cov.:

AF XY:

0.610

AC XY:

45352

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.594

AC:

24640

AN:

41466

American (AMR)

AF:

0.637

AC:

9735

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.703

AC:

2442

AN:

3472

East Asian (EAS)

AF:

0.637

AC:

3293

AN:

5166

South Asian (SAS)

AF:

0.425

AC:

2047

AN:

4816

European-Finnish (FIN)

AF:

0.569

AC:

6017

AN:

10582

Middle Eastern (MID)

AF:

0.661

AC:

193

AN:

292

European-Non Finnish (NFE)

AF:

0.639

AC:

43478

AN:

67994

Other (OTH)

AF:

0.632

AC:

1336

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1855

3711

5566

7422

9277

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

774

1548

2322

3096

3870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.623

Hom.:

15149

Bravo

AF:

0.627

Asia WGS

AF:

0.510

AC:

1771

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.4

(source)

DANN

Benign

0.47

PhyloP100

-0.70

PromoterAI

-0.024

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over