dbSNP rs840409: AMACR:c.739+3803C>G (chr5-33994838-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_014324.6(AMACR):c.739+3803C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0909 in 152,132 control chromosomes in the GnomAD database, including 697 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 0.091 ( 697 hom., cov: 32)

Consequence

AMACR
NM_014324.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.69

Publications

4 publications found

Variant links:

Genes affected

AMACR (HGNC:451): (alpha-methylacyl-CoA racemase) This gene encodes a racemase. The encoded enzyme interconverts pristanoyl-CoA and C27-bile acylCoAs between their (R)- and (S)-stereoisomers. The conversion to the (S)-stereoisomers is necessary for degradation of these substrates by peroxisomal beta-oxidation. Encoded proteins from this locus localize to both mitochondria and peroxisomes. Mutations in this gene may be associated with adult-onset sensorimotor neuropathy, pigmentary retinopathy, and adrenomyeloneuropathy due to defects in bile acid synthesis. Alternatively spliced transcript variants have been described. Read-through transcription also exists between this gene and the upstream neighboring C1QTNF3 (C1q and tumor necrosis factor related protein 3) gene. [provided by RefSeq, Mar 2011]

AMACR links:

C1QTNF3-AMACR (HGNC:49198): (C1QTNF3-AMACR readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring C1q and tumor necrosis factor related protein 3 (C1QTNF3) and alpha-methylacyl-CoA racemase (AMACR) genes on chromosome 5. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus not likely to produce a protein product. [provided by RefSeq, Mar 2011]

C1QTNF3-AMACR links:

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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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
AMACR	NM_014324.6 link	c.739+3803C>G	intron_variant	Intron 4 of 4	ENST00000335606.11	NP_055139.4
AMACR	NM_001167595.2 link	c.739+3803C>G	intron_variant	Intron 4 of 5		NP_001161067.1
AMACR	NM_203382.3 link	c.578+3803C>G	intron_variant	Intron 3 of 3		NP_976316.1
C1QTNF3-AMACR	NR_037951.1 link	n.1095+3803C>G	intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMACR	ENST00000335606.11 link	c.739+3803C>G		intron_variant	Intron 4 of 4	1	NM_014324.6	ENSP00000334424.6
C1QTNF3-AMACR	ENST00000382079.3 link	n.*165+3803C>G		intron_variant	Intron 8 of 8	2		ENSP00000371511.3

Frequencies

GnomAD3 genomes

AF:

0.0910

AC:

13830

AN:

152014

Hom.:

696

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0585

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.0616

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.175

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.0928

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0909

AC:

13836

AN:

152132

Hom.:

697

Cov.:

AF XY:

0.0922

AC XY:

6856

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.0587

AC:

2437

AN:

41512

American (AMR)

AF:

0.0615

AC:

940

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

523

AN:

3468

East Asian (EAS)

AF:

0.175

AC:

905

AN:

5166

South Asian (SAS)

AF:

0.135

AC:

650

AN:

4814

European-Finnish (FIN)

AF:

0.104

AC:

1105

AN:

10588

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.102

AC:

6946

AN:

67980

Other (OTH)

AF:

0.0909

AC:

192

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

628

1256

1884

2512

3140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

328

492

656

820

<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:

0.0938

Hom.:

Bravo

AF:

0.0865

Asia WGS

AF:

0.133

AC:

463

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.9

(source)

DANN

Benign

0.38

PhyloP100

1.7

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over