rs163234

Variant names:

• chr16-20640701-T-C
• rs163234
• NM_001318890.3:c.993-117A>G

Variant summary

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

The NM_001318890.3(ACSM1):​c.993-117A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 1,490,510 control chromosomes in the GnomAD database, including 121,748 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 0.48 (20177 hom., cov: 33)
  • Exomes 𝑓: 0.37 (101571 hom.)
• Consequence: ACSM1 NM_001318890.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.661
• Publications: 16 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSM1	NM_001318890.3	MANE Select	c.993-117A>G		intron	N/A	NP_001305819.1
	ACSM1	NM_052956.3		c.993-117A>G		intron	N/A	NP_443188.2
	ACSM1	NR_134918.2		n.1122-3250A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSM1	ENST00000520010.6	TSL:1 MANE Select	c.993-117A>G		intron	N/A	ENSP00000428047.1
	ACSM1	ENST00000307493.8	TSL:1	c.993-117A>G		intron	N/A	ENSP00000301956.3
	ACSM1	ENST00000519745.5	TSL:1	n.*439-3250A>G		intron	N/A	ENSP00000428650.1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72298 AN: 152036 Hom.: 20126 Cov.: 33

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.447

GnomAD4 exome AF: 0.367 AC: 491743 AN: 1338356 Hom.: 101571 AF XY: 0.373 AC XY: 243755 AN XY: 654350

African (AFR) AF: 0.760 AC: 22787 AN: 29982

American (AMR) AF: 0.376 AC: 10556 AN: 28042

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 10630 AN: 21344

East Asian (EAS) AF: 0.888 AC: 32037 AN: 36058

South Asian (SAS) AF: 0.572 AC: 39784 AN: 69612

European-Finnish (FIN) AF: 0.316 AC: 14626 AN: 46282

Middle Eastern (MID) AF: 0.480 AC: 2289 AN: 4764

European-Non Finnish (NFE) AF: 0.321 AC: 336026 AN: 1046900

Other (OTH) AF: 0.416 AC: 23008 AN: 55372

GnomAD4 genome AF: 0.476 AC: 72411 AN: 152154 Hom.: 20177 Cov.: 33 AF XY: 0.478 AC XY: 35524 AN XY: 74384

African (AFR) AF: 0.744 AC: 30891 AN: 41514

American (AMR) AF: 0.386 AC: 5895 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1771 AN: 3468

East Asian (EAS) AF: 0.856 AC: 4433 AN: 5178

South Asian (SAS) AF: 0.573 AC: 2768 AN: 4828

European-Finnish (FIN) AF: 0.319 AC: 3374 AN: 10590

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

European-Non Finnish (NFE) AF: 0.323 AC: 21938 AN: 67974

Other (OTH) AF: 0.451 AC: 951 AN: 2108

Alfa AF: 0.372 Hom.: 7118

Bravo AF: 0.491

Asia WGS AF: 0.686 AC: 2382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.5
DANN	Benign	0.44
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs163234; hg19: chr16-20652023;