rs26232

Variant names:

• chr5-103261019-C-T
• rs26232
• NM_033211.4:c.-114+2123C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033211.4(MACIR):​c.-114+2123C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,010 control chromosomes in the GnomAD database, including 6,617 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 0.29 (6617 hom., cov: 33)
• Consequence: MACIR NM_033211.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206
• Publications: 75 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACIR	NM_033211.4	c.-114+2123C>T		intron_variant	Intron 1 of 2	ENST00000319933.7	NP_149988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACIR	ENST00000319933.7	c.-114+2123C>T		intron_variant	Intron 1 of 2	1	NM_033211.4	ENSP00000326110.2
MACIR	ENST00000510890.1	c.-114+1228C>T		intron_variant	Intron 1 of 2	2		ENSP00000421270.1
MACIR	ENST00000515669.5	c.-114+1833C>T		intron_variant	Intron 1 of 2	3		ENSP00000422836.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44812 AN: 151894 Hom.: 6611 Cov.: 33

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.295

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.295 AC: 44839 AN: 152010 Hom.: 6617 Cov.: 33 AF XY: 0.291 AC XY: 21593 AN XY: 74320

African (AFR) AF: 0.291 AC: 12052 AN: 41412

American (AMR) AF: 0.254 AC: 3884 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1049 AN: 3472

East Asian (EAS) AF: 0.265 AC: 1369 AN: 5168

South Asian (SAS) AF: 0.172 AC: 829 AN: 4824

European-Finnish (FIN) AF: 0.300 AC: 3162 AN: 10554

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21543 AN: 67982

Other (OTH) AF: 0.293 AC: 618 AN: 2112

Alfa AF: 0.304 Hom.: 22868

Bravo AF: 0.291

Asia WGS AF: 0.217 AC: 754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	9.2
DANN	Benign	0.83
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs26232; hg19: chr5-102596720;