rs7721230

Positions:

• chr5-33992424-A-G
• chr5-33992424-A-T

Variant summary

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

The NM_014324.6(AMACR):​c.740-2922T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 150,922 control chromosomes in the GnomAD database, including 19,713 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 0.49 (19713 hom., cov: 31)
• Consequence: AMACR NM_014324.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMACR	NM_014324.6	c.740-2922T>C		intron_variant		ENST00000335606.11
C1QTNF3-AMACR	NR_037951.1	n.1096-2922T>C		intron_variant, non_coding_transcript_variant
AMACR	NM_001167595.2	c.740-2922T>C		intron_variant
AMACR	NM_203382.3	c.579-2922T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMACR	ENST00000335606.11	c.740-2922T>C		intron_variant		1	NM_014324.6	P1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73238 AN: 150822 Hom.: 19711 Cov.: 31

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.485 AC: 73256 AN: 150922 Hom.: 19713 Cov.: 31 AF XY: 0.483 AC XY: 35614 AN XY: 73792

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.608

Gnomad4 OTH AF: 0.463

Alfa AF: 0.539 Hom.: 2849

Bravo AF: 0.469

Asia WGS AF: 0.234 AC: 815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.79

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: rs7721230; hg19: chr5-33992529;