rs433598

chr16-20668884-C-T

Variant summary

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

The NM_001318890.3(ACSM1):c.912+943G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 151,958 control chromosomes in the GnomAD database, including 20,991 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 0.49 (20991 hom., cov: 31)
• Consequence: ACSM1 NM_001318890.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSM1	NM_001318890.3	c.912+943G>A		intron_variant		ENST00000520010.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSM1	ENST00000520010.6	c.912+943G>A		intron_variant		1	NM_001318890.3	P1

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74464 AN: 151840 Hom.: 20940 Cov.: 31

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.491 AC: 74573 AN: 151958 Hom.: 20991 Cov.: 31 AF XY: 0.494 AC XY: 36658 AN XY: 74248

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.858

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.458

Alfa AF: 0.375 Hom.: 26278

Bravo AF: 0.502

Asia WGS AF: 0.694 AC: 2408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	3.8
Dann	Benign	0.77

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: rs433598; hg19: chr16-20680206;