rs12027135

Positions:

• chr1-25449242-A-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACO1	NM_018202.6	c.349+308A>T		intron_variant		ENST00000374343.5
MACO1	NM_001282564.2	c.349+308A>T		intron_variant
MACO1	XM_005245931.3	c.349+308A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACO1	ENST00000374343.5	c.349+308A>T		intron_variant		1	NM_018202.6	P1
MACO1	ENST00000399766.7	c.349+308A>T		intron_variant		1
MACO1	ENST00000647928.1	c.349+308A>T		intron_variant, NMD_transcript_variant
MACO1	ENST00000470035.1	n.42+308A>T		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.460

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.486

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.60

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: rs12027135; hg19: chr1-25775733;