rs234993

Positions:

• chr16-20636322-T-C

Variant summary

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

The NM_001318890.3(ACSM1):​c.1299+417A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0798 in 152,238 control chromosomes in the GnomAD database, including 631 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 0.080 (631 hom., cov: 31)
• Consequence: ACSM1 NM_001318890.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSM1	NM_001318890.3	c.1299+417A>G		intron_variant		ENST00000520010.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSM1	ENST00000520010.6	c.1299+417A>G		intron_variant		1	NM_001318890.3	P1

Frequencies

GnomAD3 genomes AF: 0.0799 AC: 12155 AN: 152120 Hom.: 630 Cov.: 31

Gnomad AFR AF: 0.0347

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.0573

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0995

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0916

Gnomad OTH AF: 0.0831

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

GnomAD4 genome AF: 0.0798 AC: 12152 AN: 152238 Hom.: 631 Cov.: 31 AF XY: 0.0804 AC XY: 5981 AN XY: 74426

Gnomad4 AFR AF: 0.0347

Gnomad4 AMR AF: 0.0572

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.0995

Gnomad4 NFE AF: 0.0916

Gnomad4 OTH AF: 0.0818

Alfa AF: 0.0859 Hom.: 592

Bravo AF: 0.0724

Asia WGS AF: 0.151 AC: 522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.4
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs234993; hg19: chr16-20647644;