chr16-20556016-T-C

Variant names:

• chr16-20556016-T-C
• rs12324972
• NM_001105069.2:c.389-540A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105069.2. 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
	ACSM2B	NM_001105069.2	MANE Select	c.389-540A>G		intron	N/A	NP_001098539.1
	ACSM2B	NM_182617.4		c.389-540A>G		intron	N/A	NP_872423.3
	ACSM2B	NM_001410902.1		c.152-540A>G		intron	N/A	NP_001397831.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSM2B	ENST00000329697.10	TSL:1 MANE Select	c.389-540A>G		intron	N/A	ENSP00000327453.6
	ACSM2B	ENST00000414188.6	TSL:1	c.389-540A>G		intron	N/A	ENSP00000390378.3
	ACSM2B	ENST00000567001.5	TSL:1	c.389-540A>G		intron	N/A	ENSP00000456378.1

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

African (AFR) AF: 0.268 AC: 11077 AN: 41298

American (AMR) AF: 0.666 AC: 10144 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2213 AN: 3464

East Asian (EAS) AF: 0.131 AC: 675 AN: 5162

South Asian (SAS) AF: 0.466 AC: 2242 AN: 4808

European-Finnish (FIN) AF: 0.723 AC: 7618 AN: 10534

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.740 AC: 50296 AN: 67982

Other (OTH) AF: 0.600 AC: 1265 AN: 2108

Alfa AF: 0.595 Hom.: 8727

Bravo AF: 0.554

Asia WGS AF: 0.333 AC: 1159 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.8
DANN	Benign	0.73
PhyloP100		0.029
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12324972; hg19: chr16-20567338;