16-20663170-G-C

Position:

• chr16-20663170-G-C

Variant summary

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

The NM_001318890.3(ACSM1):​c.913-1297C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0814 in 152,194 control chromosomes in the GnomAD database, including 644 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 0.081 (644 hom., cov: 32)
• Consequence: ACSM1 NM_001318890.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.229

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=-0.94).
• 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	Protein	UniProt
ACSM1	NM_001318890.3	c.913-1297C>G		intron_variant		ENST00000520010.6	NP_001305819.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSM1	ENST00000520010.6	c.913-1297C>G		intron_variant		1	NM_001318890.3	ENSP00000428047	P1

Frequencies

GnomAD3 genomes AF: 0.0815 AC: 12392 AN: 152076 Hom.: 643 Cov.: 32

Gnomad AFR AF: 0.0387

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.0580

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0921

Gnomad OTH AF: 0.0845

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

GnomAD4 genome AF: 0.0814 AC: 12389 AN: 152194 Hom.: 644 Cov.: 32 AF XY: 0.0820 AC XY: 6103 AN XY: 74386

Gnomad4 AFR AF: 0.0387

Gnomad4 AMR AF: 0.0580

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.0921

Gnomad4 OTH AF: 0.0827

Alfa AF: 0.0301 Hom.: 25

Bravo AF: 0.0740

Asia WGS AF: 0.150 AC: 519 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.9
DANN	Benign	0.39

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: rs151222; hg19: chr16-20674492;