Variant chr16-20548455-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001105069.2(ACSM2B):c.913A>G(p.Ile305Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00748 in 1,612,000 control chromosomes in the GnomAD database, including 1,009 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 522 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 487 hom. )

Consequence

ACSM2B
NM_001105069.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.12

Variant links:

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]

ACSM2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019419491).

BP6

Variant 16-20548455-T-C is Benign according to our data. Variant chr16-20548455-T-C is described in ClinVar as [Benign]. Clinvar id is 776988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSM2B	NM_001105069.2 linkuse as main transcript	c.913A>G	p.Ile305Val	missense_variant	7/14	ENST00000329697.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSM2B	ENST00000329697.10 linkuse as main transcript	c.913A>G	p.Ile305Val	missense_variant	7/14	1	NM_001105069.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0444

AC:

6744

AN:

151914

Hom.:

519

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.0244

GnomAD3 exomes

AF:

0.00873

AC:

2190

AN:

250718

Hom.:

203

AF XY:

0.00659

AC XY:

893

AN XY:

135540

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.00611

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000273

Gnomad OTH exome

AF:

0.00408

GnomAD4 exome

AF:

0.00361

AC:

5270

AN:

1459968

Hom.:

487

Cov.:

AF XY:

0.00311

AC XY:

2257

AN XY:

726414

show subpopulations

Gnomad4 AFR exome

AF:

0.130

Gnomad4 AMR exome

AF:

0.00746

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000147

Gnomad4 OTH exome

AF:

0.00877

GnomAD4 genome

AF:

0.0446

AC:

6780

AN:

152032

Hom.:

522

Cov.:

AF XY:

0.0443

AC XY:

3290

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.156

Gnomad4 AMR

AF:

0.0163

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.0241

Alfa

AF:

0.0142

Hom.:

Bravo

AF:

0.0510

ESP6500AA

AF:

0.0971

AC:

427

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00972

AC:

1180

EpiCase

AF:

0.000764

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 17, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.62

CADD

Benign

8.4

DANN

Benign

0.41

DEOGEN2

Benign

0.0095

T;T;.;T;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.51

.;T;T;.;.;T

MetaRNN

Benign

0.0019

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.91

L;L;.;L;L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.74

N;.;N;N;N;.

REVEL

Benign

0.058

Sift

Benign

0.15

T;.;T;T;T;.

Sift4G

Benign

0.24

T;T;T;T;T;T

Polyphen

0.033

B;B;.;B;B;.

Vest4

0.23

MVP

0.30

MPC

0.89

ClinPred

0.0042

GERP RS

-0.040

Varity_R

0.058

gMVP

0.40

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over