rs12027135

Variant names:

• chr1-25449242-A-T
• rs12027135
• NM_018202.6:c.349+308A>T

Variant summary

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

The NM_018202.6(MACO1):​c.349+308A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 151,860 control chromosomes in the GnomAD database, including 19,024 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 0.50 (19024 hom., cov: 31)
• Consequence: MACO1 NM_018202.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363
• Publications: 88 publications found

Genes affected

MACO1 (HGNC:25572): (macoilin 1) Predicted to enable actin filament binding activity and microtubule binding activity. Involved in neuronal signal transduction. Located in rough endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018202.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACO1	NM_018202.6	MANE Select	c.349+308A>T		intron	N/A	NP_060672.2
	MACO1	NM_001282564.2		c.349+308A>T		intron	N/A	NP_001269493.1	Q8N5G2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACO1	ENST00000374343.5	TSL:1 MANE Select	c.349+308A>T		intron	N/A	ENSP00000363463.4	Q8N5G2-1
	MACO1	ENST00000399766.7	TSL:1	c.349+308A>T		intron	N/A	ENSP00000382668.3	Q8N5G2-3
	MACO1	ENST00000897268.1		c.349+308A>T		intron	N/A	ENSP00000567327.1

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75239 AN: 151742 Hom.: 19008 Cov.: 31

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.496 AC: 75285 AN: 151860 Hom.: 19024 Cov.: 31 AF XY: 0.491 AC XY: 36437 AN XY: 74236

African (AFR) AF: 0.460 AC: 19038 AN: 41400

American (AMR) AF: 0.495 AC: 7557 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1618 AN: 3470

East Asian (EAS) AF: 0.274 AC: 1416 AN: 5172

South Asian (SAS) AF: 0.326 AC: 1567 AN: 4810

European-Finnish (FIN) AF: 0.535 AC: 5636 AN: 10528

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.542 AC: 36813 AN: 67926

Other (OTH) AF: 0.486 AC: 1023 AN: 2104

Alfa AF: 0.522 Hom.: 11663

Bravo AF: 0.492

Asia WGS AF: 0.291 AC: 1014 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.60
PhyloP100		0.36
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: rs12027135; hg19: chr1-25775733;