rs6497501

Positions:

• chr16-20554263-G-A
• chr16-20554263-G-C
• chr16-20554263-G-T

Variant summary

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

The NM_001105069.2(ACSM2B):​c.597-343C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 450,052 control chromosomes in the GnomAD database, including 31,918 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 0.38 (14108 hom., cov: 33)
  • Exomes 𝑓: 0.31 (17810 hom.)
• Consequence: ACSM2B NM_001105069.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSM2B	NM_001105069.2	c.597-343C>T		intron_variant		ENST00000329697.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSM2B	ENST00000329697.10	c.597-343C>T		intron_variant		1	NM_001105069.2	P1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58004 AN: 151948 Hom.: 14065 Cov.: 33

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.349

GnomAD4 exome AF: 0.308 AC: 91740 AN: 297986 Hom.: 17810 AF XY: 0.317 AC XY: 53483 AN XY: 168802

Gnomad4 AFR exome AF: 0.639

Gnomad4 AMR exome AF: 0.315

Gnomad4 ASJ exome AF: 0.290

Gnomad4 EAS exome AF: 0.875

Gnomad4 SAS exome AF: 0.425

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.225

Gnomad4 OTH exome AF: 0.313

GnomAD4 genome AF: 0.382 AC: 58107 AN: 152066 Hom.: 14108 Cov.: 33 AF XY: 0.385 AC XY: 28650 AN XY: 74346

Gnomad4 AFR AF: 0.641

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.868

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.354

Alfa AF: 0.259 Hom.: 7493

Bravo AF: 0.397

Asia WGS AF: 0.635 AC: 2200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.9
DANN	Benign	0.55

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: rs6497501; hg19: chr16-20565585;