rs873308

Positions:

• chr1-25432164-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018202.6(MACO1):​c.80+986G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 152,070 control chromosomes in the GnomAD database, including 15,977 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 (15977 hom., cov: 33)
• Consequence: MACO1 NM_018202.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACO1	NM_018202.6	c.80+986G>A		intron_variant		ENST00000374343.5
MACO1	NM_001282564.2	c.80+986G>A		intron_variant
MACO1	XM_005245931.3	c.80+986G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACO1	ENST00000374343.5	c.80+986G>A		intron_variant		1	NM_018202.6	P1
MACO1	ENST00000399766.7	c.80+986G>A		intron_variant		1
MACO1	ENST00000647928.1	c.80+986G>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67248 AN: 151952 Hom.: 15958 Cov.: 33

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.442 AC: 67288 AN: 152070 Hom.: 15977 Cov.: 33 AF XY: 0.440 AC XY: 32656 AN XY: 74298

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.431

Alfa AF: 0.500 Hom.: 9015

Bravo AF: 0.430

Asia WGS AF: 0.278 AC: 967 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs873308; hg19: chr1-25758655;