Genetic Variant NM_006770.4: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:

Genome browser will be placed here

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.

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.97+123T>C		intron	N/A	NP_006761.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCO	ENST00000327097.5	TSL:1 MANE Select	c.97+123T>C		intron	N/A	ENSP00000318916.4
	MARCO	ENST00000412481.1	TSL:4	c.-271+123T>C		intron	N/A	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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over