Genetic Variant MACIR:c.*2086C>T (chr5-103278626-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_033211.4(MACIR):c.*2086C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 166,894 control chromosomes in the GnomAD database, including 17,447 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 0.44 ( 16574 hom., cov: 32)

Exomes 𝑓: 0.34 ( 873 hom. )

Consequence

MACIR
NM_033211.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.118

Publications

16 publications found

Variant links:

Genes affected

MACIR (HGNC:25052): (macrophage immunometabolism regulator) This gene, MACIR (previously known as C5orf30), has been associated with rheumatoid arthritis, functioning as a negative regulator of tissue damage and modulating the activity of synovial fibroblasts and macrophages. The encoded protein is highly conserved in vertebrate genomes but has no significant similarity to any other human protein. [provided by RefSeq, Dec 2019]

MACIR 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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MACIR	NM_033211.4 link	c.*2086C>T	3_prime_UTR_variant	Exon 3 of 3	ENST00000319933.7	NP_149988.1	Q96GV9
MACIR	NM_001316968.2 link	c.*2086C>T	3_prime_UTR_variant	Exon 3 of 3		NP_001303897.1	Q96GV9
MACIR	NM_001316969.2 link	c.*2086C>T	3_prime_UTR_variant	Exon 3 of 3		NP_001303898.1	Q96GV9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACIR	ENST00000319933.7 link	c.*2086C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_033211.4	ENSP00000326110.2		Q96GV9

Frequencies

GnomAD3 genomes

AF:

0.441

AC:

66968

AN:

151884

Hom.:

16520

Cov.:

show subpopulations

Gnomad AFR

AF:

0.684

Gnomad AMI

AF:

0.280

Gnomad AMR

AF:

0.383

Gnomad ASJ

AF:

0.361

Gnomad EAS

AF:

0.289

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.361

Gnomad OTH

AF:

0.413

GnomAD4 exome

AF:

0.343

AC:

5114

AN:

14892

Hom.:

873

Cov.:

AF XY:

0.345

AC XY:

2443

AN XY:

7074

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.343

AC:

5042

AN:

14700

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.372

AC:

AN:

Other (OTH)

AF:

0.378

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

196

391

587

782

978

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.441

AC:

67082

AN:

152002

Hom.:

16574

Cov.:

AF XY:

0.433

AC XY:

32138

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.684

AC:

28366

AN:

41470

American (AMR)

AF:

0.384

AC:

5857

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.361

AC:

1252

AN:

3466

East Asian (EAS)

AF:

0.289

AC:

1493

AN:

5168

South Asian (SAS)

AF:

0.209

AC:

1005

AN:

4818

European-Finnish (FIN)

AF:

0.316

AC:

3334

AN:

10552

Middle Eastern (MID)

AF:

0.340

AC:

100

AN:

294

European-Non Finnish (NFE)

AF:

0.361

AC:

24556

AN:

67948

Other (OTH)

AF:

0.410

AC:

864

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1769

3538

5308

7077

8846

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

584

1168

1752

2336

2920

<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:

0.403

Hom.:

10789

Bravo

AF:

0.459

Asia WGS

AF:

0.289

AC:

1006

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.6

(source)

DANN

Benign

0.74

PhyloP100

0.12

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over