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GeneBe

20-34914359-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_018677.4(ACSS2):c.756C>T(p.His252=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00206 in 1,613,900 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0020 ( 13 hom. )

Consequence

ACSS2
NM_018677.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.480
Variant links:
Genes affected
ACSS2 (HGNC:15814): (acyl-CoA synthetase short chain family member 2) This gene encodes a cytosolic enzyme that catalyzes the activation of acetate for use in lipid synthesis and energy generation. The protein acts as a monomer and produces acetyl-CoA from acetate in a reaction that requires ATP. Expression of this gene is regulated by sterol regulatory element-binding proteins, transcription factors that activate genes required for the synthesis of cholesterol and unsaturated fatty acids. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 20-34914359-C-T is Benign according to our data. Variant chr20-34914359-C-T is described in ClinVar as [Benign]. Clinvar id is 3043533.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.48 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ACSS2NM_018677.4 linkuse as main transcriptc.756C>T p.His252= synonymous_variant 7/18 ENST00000360596.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ACSS2ENST00000360596.7 linkuse as main transcriptc.756C>T p.His252= synonymous_variant 7/181 NM_018677.4 P4Q9NR19-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00233
AC:
355
AN:
152194
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00236
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.0166
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00181
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.00257
AC:
645
AN:
250584
Hom.:
7
AF XY:
0.00258
AC XY:
349
AN XY:
135414
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.00139
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00118
Gnomad FIN exome
AF:
0.0171
Gnomad NFE exome
AF:
0.00149
Gnomad OTH exome
AF:
0.00328
GnomAD4 exome
AF:
0.00204
AC:
2976
AN:
1461588
Hom.:
13
Cov.:
32
AF XY:
0.00203
AC XY:
1478
AN XY:
727082
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.00139
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00122
Gnomad4 FIN exome
AF:
0.0162
Gnomad4 NFE exome
AF:
0.00164
Gnomad4 OTH exome
AF:
0.00185
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00233
AC:
355
AN:
152312
Hom.:
3
Cov.:
32
AF XY:
0.00309
AC XY:
230
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.000241
Gnomad4 AMR
AF:
0.00235
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.0166
Gnomad4 NFE
AF:
0.00181
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00131
Hom.:
0
Bravo
AF:
0.00101
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00115
EpiControl
AF:
0.00148

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

ACSS2-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesMar 16, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.38
Cadd
Benign
6.8
Dann
Benign
0.55
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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.

Other links and lift over

dbSNP: rs61014667; hg19: chr20-33502162; API