rs26232

Positions:

• chr5-103261019-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MACIR	NM_033211.4	c.-114+2123C>T		intron_variant		ENST00000319933.7	NP_149988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MACIR	ENST00000319933.7	c.-114+2123C>T		intron_variant		1	NM_033211.4	ENSP00000326110	P1
MACIR	ENST00000510890.1	c.-114+1228C>T		intron_variant		2		ENSP00000421270	P1
MACIR	ENST00000515669.5	c.-114+1833C>T		intron_variant		3		ENSP00000422836	P1

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

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.293

Alfa AF: 0.304 Hom.: 9462

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

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

Other links and lift over

dbSNP: rs26232; hg19: chr5-102596720;