rs2652130

chr5-33991294-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014324.6(AMACR):c.740-1792T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,012 control chromosomes in the GnomAD database, including 2,566 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 0.17 (2566 hom., cov: 32)
• Consequence: AMACR NM_014324.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

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]

C1QTNF3-AMACR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMACR	NM_014324.6	c.740-1792T>G		intron_variant		ENST00000335606.11
C1QTNF3-AMACR	NR_037951.1	n.1096-1792T>G		intron_variant, non_coding_transcript_variant
AMACR	NM_001167595.2	c.740-1792T>G		intron_variant
AMACR	NM_203382.3	c.579-1792T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMACR	ENST00000335606.11	c.740-1792T>G		intron_variant		1	NM_014324.6	P1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25714 AN: 151894 Hom.: 2560 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.169 AC: 25750 AN: 152012 Hom.: 2566 Cov.: 32 AF XY: 0.173 AC XY: 12845 AN XY: 74296

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.162

Alfa AF: 0.125 Hom.: 1732

Bravo AF: 0.166

Asia WGS AF: 0.343 AC: 1191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.5
Dann	Benign	0.74

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

Other links and lift over

dbSNP: rs2652130; hg19: chr5-33991399;