16-20556016-T-C

Variant summary

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

The NM_001105069.2(ACSM2B):c.389-540A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 151,802 control chromosomes in the GnomAD database, including 28,266 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 0.57 (28266 hom., cov: 30)
• Consequence: ACSM2B NM_001105069.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290

Genes affected

ACSM2B (HGNC:30931): (acyl-CoA synthetase medium chain family member 2B) Enables benzoate-CoA ligase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Located in mitochondrion. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSM2B	NM_001105069.2	c.389-540A>G		intron_variant		ENST00000329697.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSM2B	ENST00000329697.10	c.389-540A>G		intron_variant		1	NM_001105069.2	P1

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86381 AN: 151684 Hom.: 28270 Cov.: 30

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.569 AC: 86385 AN: 151802 Hom.: 28266 Cov.: 30 AF XY: 0.566 AC XY: 41976 AN XY: 74168

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.666

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.466

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.740

Gnomad4 OTH AF: 0.600

Alfa AF: 0.595 Hom.: 3595

Bravo AF: 0.554

Asia WGS AF: 0.333 AC: 1159 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	5.8
Dann	Benign	0.73

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: rs12324972; hg19: chr16-20567338;