Genetic Variant NM_032592.4:c.871C>T (chr11-44079568-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_032592.4(ACCS):c.871C>T(p.Leu291Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,611,620 control chromosomes in the GnomAD database, including 11,136 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 0.12 ( 1137 hom., cov: 32)

Exomes 𝑓: 0.12 ( 9999 hom. )

Consequence

ACCS
NM_032592.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.03

Publications

11 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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BP7

Synonymous conserved (PhyloP=3.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACCS	NM_032592.4 link	c.871C>T	p.Leu291Leu	synonymous_variant	Exon 10 of 15	ENST00000263776.9	NP_115981.1	Q96QU6-1A0A0S2Z622

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACCS	ENST00000263776.9 link	c.871C>T	p.Leu291Leu	synonymous_variant	Exon 10 of 15	1	NM_032592.4	ENSP00000263776.8		Q96QU6-1

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18551

AN:

152072

Hom.:

1139

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.159

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.110

Gnomad SAS

AF:

0.0966

Gnomad FIN

AF:

0.0959

Gnomad MID

AF:

0.188

Gnomad NFE

AF:

0.124

Gnomad OTH

AF:

0.136

GnomAD2 exomes

AF:

0.110

AC:

27148

AN:

247490

AF XY:

0.111

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.0745

Gnomad ASJ exome

AF:

0.119

Gnomad EAS exome

AF:

0.110

Gnomad FIN exome

AF:

0.0873

Gnomad NFE exome

AF:

0.125

Gnomad OTH exome

AF:

0.120

GnomAD4 exome

AF:

0.115

AC:

168105

AN:

1459430

Hom.:

9999

Cov.:

AF XY:

0.115

AC XY:

83548

AN XY:

725674

show subpopulations

African (AFR)

AF:

0.134

AC:

4470

AN:

33452

American (AMR)

AF:

0.0767

AC:

3420

AN:

44580

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

3125

AN:

26110

East Asian (EAS)

AF:

0.107

AC:

4261

AN:

39682

South Asian (SAS)

AF:

0.0979

AC:

8372

AN:

85528

European-Finnish (FIN)

AF:

0.0920

AC:

4909

AN:

53342

Middle Eastern (MID)

AF:

0.162

AC:

863

AN:

5318

European-Non Finnish (NFE)

AF:

0.118

AC:

131355

AN:

1111108

Other (OTH)

AF:

0.122

AC:

7330

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

7522

15044

22565

30087

37609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4636

9272

13908

18544

23180

<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:

0.122

AC:

18551

AN:

152190

Hom.:

1137

Cov.:

AF XY:

0.122

AC XY:

9041

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.134

AC:

5545

AN:

41496

American (AMR)

AF:

0.104

AC:

1591

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.126

AC:

437

AN:

3470

East Asian (EAS)

AF:

0.111

AC:

573

AN:

5178

South Asian (SAS)

AF:

0.0965

AC:

465

AN:

4820

European-Finnish (FIN)

AF:

0.0959

AC:

1018

AN:

10616

Middle Eastern (MID)

AF:

0.178

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.124

AC:

8443

AN:

68002

Other (OTH)

AF:

0.134

AC:

282

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

844

1688

2532

3376

4220

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

210

420

630

840

1050

<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:

0.120

Hom.:

948

Bravo

AF:

0.123

Asia WGS

AF:

0.0940

AC:

328

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

3.0

Mutation Taster

=93/7

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over