Genetic Variant ACCS:c.-263G>T (chr11-44066439-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032592.4(ACCS):c.-263G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0873 in 152,402 control chromosomes in the GnomAD database, including 856 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 0.087 ( 855 hom., cov: 33)

Exomes 𝑓: 0.10 ( 1 hom. )

Consequence

ACCS
NM_032592.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.103

Publications

53 publications found

Variant links:

Genes affected

ACCS (HGNC:23989): (1-aminocyclopropane-1-carboxylate synthase homolog (inactive)) Enables identical protein binding activity. Predicted to be involved in biosynthetic process. [provided by Alliance of Genome Resources, Apr 2022]

ACCS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032592.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACCS	NM_032592.4	MANE Select	c.-263G>T		5_prime_UTR	Exon 1 of 15	NP_115981.1
	ACCS	NM_001127219.2		c.-1+117G>T		intron	N/A	NP_001120691.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ACCS	ENST00000263776.9	TSL:1 MANE Select	c.-263G>T	5_prime_UTR	Exon 1 of 15	ENSP00000263776.8
ACCS	ENST00000894383.1		c.-263G>T	5_prime_UTR	Exon 1 of 15	ENSP00000564442.1
ACCS	ENST00000894381.1		c.-263G>T	5_prime_UTR	Exon 1 of 14	ENSP00000564440.1

Frequencies

GnomAD3 genomes

AF:

0.0874

AC:

13294

AN:

152184

Hom.:

856

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0222

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.0892

Gnomad ASJ

AF:

0.223

Gnomad EAS

AF:

0.269

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.0767

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.103

GnomAD4 exome

AF:

0.100

AC:

AN:

100

Hom.:

Cov.:

AF XY:

0.0875

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.100

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.111

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0872

AC:

13288

AN:

152302

Hom.:

855

Cov.:

AF XY:

0.0885

AC XY:

6590

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0222

AC:

922

AN:

41584

American (AMR)

AF:

0.0891

AC:

1363

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

774

AN:

3472

East Asian (EAS)

AF:

0.269

AC:

1389

AN:

5168

South Asian (SAS)

AF:

0.110

AC:

530

AN:

4824

European-Finnish (FIN)

AF:

0.0767

AC:

814

AN:

10614

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.106

AC:

7200

AN:

68018

Other (OTH)

AF:

0.102

AC:

215

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

626

1253

1879

2506

3132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

312

468

624

780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0951

Hom.:

634

Bravo

AF:

0.0900

Asia WGS

AF:

0.157

AC:

545

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.2

(source)

DANN

Benign

0.81

PhyloP100

0.10

PromoterAI

0.64

Over-expression

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over