16-20548432-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001105069.2(ACSM2B):c.936T>C(p.Pro312=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00367 in 1,611,690 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (88 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (68 hom.)
• Consequence: ACSM2B NM_001105069.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0760

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 16-20548432-A-G is Benign according to our data. Variant chr16-20548432-A-G is described in ClinVar as [Benign]. Clinvar id is 786754.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.076 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSM2B	NM_001105069.2	c.936T>C	p.Pro312=	synonymous_variant	7/14	ENST00000329697.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSM2B	ENST00000329697.10	c.936T>C	p.Pro312=	synonymous_variant	7/14	1	NM_001105069.2	P1

Frequencies

GnomAD3 genomes AF: 0.0206 AC: 3128 AN: 151864 Hom.: 88 Cov.: 32

Gnomad AFR AF: 0.0640

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00845

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0135

Gnomad FIN AF: 0.0146

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00171

Gnomad OTH AF: 0.00766

GnomAD3 exomes AF: 0.00236 AC: 592 AN: 250382 Hom.: 27 AF XY: 0.00206 AC XY: 279 AN XY: 135322

Gnomad AFR exome AF: 0.0221

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.000653

Gnomad SAS exome AF: 0.00362

Gnomad FIN exome AF: 0.000840

Gnomad NFE exome AF: 0.000282

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00191 AC: 2788 AN: 1459710 Hom.: 68 Cov.: 31 AF XY: 0.00205 AC XY: 1490 AN XY: 726102

Gnomad4 AFR exome AF: 0.0251

Gnomad4 AMR exome AF: 0.00193

Gnomad4 ASJ exome AF: 0.000498

Gnomad4 EAS exome AF: 0.000605

Gnomad4 SAS exome AF: 0.00817

Gnomad4 FIN exome AF: 0.00976

Gnomad4 NFE exome AF: 0.000364

Gnomad4 OTH exome AF: 0.00335

GnomAD4 genome AF: 0.0206 AC: 3134 AN: 151980 Hom.: 88 Cov.: 32 AF XY: 0.0210 AC XY: 1557 AN XY: 74312

Gnomad4 AFR AF: 0.0639

Gnomad4 AMR AF: 0.00844

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0137

Gnomad4 FIN AF: 0.0146

Gnomad4 NFE AF: 0.00171

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.00149 Hom.: 1

Bravo AF: 0.0217

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 17, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	2.7
Dann	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs141915122; hg19: chr16-20559754; COSMIC: COSV100312338; COSMIC: COSV100312338;