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

Variant summary

Our verdict is Benign. Variant got -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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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

Gnomad4 AFR exome

AF:

0.500

Gnomad4 AMR exome

AF:

0.500

Gnomad4 EAS exome

AF:

0.250

Gnomad4 FIN exome

AF:

0.343

Gnomad4 NFE exome

AF:

0.372

Gnomad4 OTH exome

AF:

0.378

GnomAD4 genome

AF:

0.441

AC:

67082

AN:

152002

Hom.:

16574

Cov.:

AF XY:

0.433

AC XY:

32138

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.684

Gnomad4 AMR

AF:

0.384

Gnomad4 ASJ

AF:

0.361

Gnomad4 EAS

AF:

0.289

Gnomad4 SAS

AF:

0.209

Gnomad4 FIN

AF:

0.316

Gnomad4 NFE

AF:

0.361

Gnomad4 OTH

AF:

0.410

Alfa

AF:

0.382

Hom.:

6863

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

DANN

Benign

0.74

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over