rs163274

Positions:

• chr16-20661013-A-G

Variant summary

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

The NM_001318890.3(ACSM1):​c.992+781T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 152,044 control chromosomes in the GnomAD database, including 18,971 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 0.46 (18971 hom., cov: 32)
• Consequence: ACSM1 NM_001318890.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730

Genes affected

ACSM1 (HGNC:18049): (acyl-CoA synthetase medium chain family member 1) Enables CoA-ligase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACSM3 (HGNC:10522): (acyl-CoA synthetase medium chain family member 3) Enables butyrate-CoA ligase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Located in mitochondrion. Implicated in IgA glomerulonephritis. Biomarker of ulcerative colitis. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSM1	NM_001318890.3	c.992+781T>C		intron_variant		ENST00000520010.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSM1	ENST00000520010.6	c.992+781T>C		intron_variant		1	NM_001318890.3	P1

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69889 AN: 151926 Hom.: 18931 Cov.: 32

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.460 AC: 69990 AN: 152044 Hom.: 18971 Cov.: 32 AF XY: 0.461 AC XY: 34252 AN XY: 74322

Gnomad4 AFR AF: 0.721

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.437

Alfa AF: 0.352 Hom.: 10252

Bravo AF: 0.478

Asia WGS AF: 0.645 AC: 2239 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.41

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: rs163274; hg19: chr16-20672335;