rs6863657

Positions:

• chr5-33994629-G-A

Variant summary

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

The NM_014324.6(AMACR):​c.739+4012C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0648 in 152,254 control chromosomes in the GnomAD database, including 462 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 0.065 (462 hom., cov: 32)
• Consequence: AMACR NM_014324.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.694

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMACR	NM_014324.6	c.739+4012C>T		intron_variant		ENST00000335606.11	NP_055139.4
C1QTNF3-AMACR	NR_037951.1	n.1095+4012C>T		intron_variant, non_coding_transcript_variant
AMACR	NM_001167595.2	c.739+4012C>T		intron_variant			NP_001161067.1
AMACR	NM_203382.3	c.578+4012C>T		intron_variant			NP_976316.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMACR	ENST00000335606.11	c.739+4012C>T		intron_variant		1	NM_014324.6	ENSP00000334424	P1

Frequencies

GnomAD3 genomes AF: 0.0649 AC: 9871 AN: 152136 Hom.: 462 Cov.: 32

Gnomad AFR AF: 0.0162

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.0384

Gnomad ASJ AF: 0.0789

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00973

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0946

Gnomad OTH AF: 0.0517

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

GnomAD4 genome AF: 0.0648 AC: 9870 AN: 152254 Hom.: 462 Cov.: 32 AF XY: 0.0644 AC XY: 4795 AN XY: 74434

Gnomad4 AFR AF: 0.0162

Gnomad4 AMR AF: 0.0384

Gnomad4 ASJ AF: 0.0789

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00953

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.0946

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0837 Hom.: 330

Bravo AF: 0.0576

Asia WGS AF: 0.00924 AC: 32 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	1.4
DANN	Benign	0.19

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: rs6863657; hg19: chr5-33994734;