chr1-155566947-G-A

Variant names:

• chr1-155566947-G-A
• rs8179271
• ENST00000456633.3:n.4228G>A

Variant summary

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

The ENST00000456633.3(ASH1L-AS1):​n.4228G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0594 in 152,030 control chromosomes in the GnomAD database, including 1,555 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 0.059 (1555 hom., cov: 31)
• Consequence: ASH1L-AS1 ENST00000456633.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320
• Publications: 8 publications found

Genes affected

ASH1L-AS1 (HGNC:44146): (ASH1L antisense RNA 1)

MSTO1 (HGNC:29678): (misato mitochondrial distribution and morphology regulator 1) Involved in mitochondrion distribution. Located in cytosol and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

MSTO1 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Broad Center for Mendelian Genomics, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000456633.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASH1L-AS1	ENST00000456633.3	TSL:2	n.4228G>A		non_coding_transcript_exon	Exon 2 of 2
	MSTO1	ENST00000697770.1		c.-379+3618G>A		intron	N/A	ENSP00000513434.1

Frequencies

GnomAD3 genomes AF: 0.0593 AC: 9010 AN: 151912 Hom.: 1549 Cov.: 31

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.0626

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0576

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

GnomAD4 genome AF: 0.0594 AC: 9023 AN: 152030 Hom.: 1555 Cov.: 31 AF XY: 0.0683 AC XY: 5076 AN XY: 74298

African (AFR) AF: 0.0133 AC: 553 AN: 41518

American (AMR) AF: 0.143 AC: 2189 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 134 AN: 3468

East Asian (EAS) AF: 0.676 AC: 3465 AN: 5126

South Asian (SAS) AF: 0.198 AC: 955 AN: 4812

European-Finnish (FIN) AF: 0.0626 AC: 662 AN: 10570

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0135 AC: 920 AN: 67968

Other (OTH) AF: 0.0556 AC: 117 AN: 2106

Alfa AF: 0.0389 Hom.: 1613

Bravo AF: 0.0699

Asia WGS AF: 0.403 AC: 1398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.42
PhyloP100		0.32

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8179271; hg19: chr1-155536738;