chr5-33991294-A-C

Variant names:

• chr5-33991294-A-C
• rs2652130
• NM_014324.6:c.740-1792T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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: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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AMACR	NM_014324.6	c.740-1792T>G		intron_variant	Intron 4 of 4	ENST00000335606.11	NP_055139.4
AMACR	NM_001167595.2	c.740-1792T>G		intron_variant	Intron 4 of 5		NP_001161067.1
AMACR	NM_203382.3	c.579-1792T>G		intron_variant	Intron 3 of 3		NP_976316.1
C1QTNF3-AMACR	NR_037951.1	n.1096-1792T>G		intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMACR	ENST00000335606.11	c.740-1792T>G		intron_variant	Intron 4 of 4	1	NM_014324.6	ENSP00000334424.6
C1QTNF3-AMACR	ENST00000382079.3	n.*166-1792T>G		intron_variant	Intron 8 of 8	2		ENSP00000371511.3

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

African (AFR) AF: 0.242 AC: 10034 AN: 41420

American (AMR) AF: 0.103 AC: 1579 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 574 AN: 3470

East Asian (EAS) AF: 0.310 AC: 1599 AN: 5158

South Asian (SAS) AF: 0.339 AC: 1631 AN: 4812

European-Finnish (FIN) AF: 0.134 AC: 1417 AN: 10574

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8427 AN: 67988

Other (OTH) AF: 0.162 AC: 343 AN: 2112

Alfa AF: 0.129 Hom.: 2357

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
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2652130; hg19: chr5-33991399;