rs163274

Variant names:

• chr16-20661013-A-G
• rs163274
• NM_001318890.3:c.992+781T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318890.3. 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
	ACSM1	NM_001318890.3	MANE Select	c.992+781T>C		intron	N/A	NP_001305819.1	Q08AH1-1
	ACSM1	NM_052956.3		c.992+781T>C		intron	N/A	NP_443188.2	Q08AH1-1
	ACSM1	NR_134918.2		n.1121+781T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSM1	ENST00000520010.6	TSL:1 MANE Select	c.992+781T>C		intron	N/A	ENSP00000428047.1	Q08AH1-1
	ACSM1	ENST00000307493.8	TSL:1	c.992+781T>C		intron	N/A	ENSP00000301956.3	Q08AH1-1
	ACSM1	ENST00000519745.5	TSL:1	n.*438+781T>C		intron	N/A	ENSP00000428650.1	Q08AH1-2

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

African (AFR) AF: 0.721 AC: 29915 AN: 41470

American (AMR) AF: 0.379 AC: 5777 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1766 AN: 3466

East Asian (EAS) AF: 0.853 AC: 4412 AN: 5172

South Asian (SAS) AF: 0.541 AC: 2606 AN: 4818

European-Finnish (FIN) AF: 0.277 AC: 2935 AN: 10586

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21310 AN: 67958

Other (OTH) AF: 0.437 AC: 923 AN: 2114

Alfa AF: 0.395 Hom.: 21020

Bravo AF: 0.478

Asia WGS AF: 0.645 AC: 2239 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.41
PhyloP100		0.073
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: rs163274; hg19: chr16-20672335;