rs1411675

Positions:

• chr9-69072136-G-A
• chr9-69072136-G-C
• chr9-69072136-G-T

Variant summary

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

The NM_000144.5(FXN):​c.483-476G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,072 control chromosomes in the GnomAD database, including 18,888 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 (18888 hom., cov: 32)
• Consequence: FXN NM_000144.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

Genes affected

FXN (HGNC:3951): (frataxin) This nuclear gene encodes a mitochondrial protein which belongs to the FRATAXIN family. The protein functions in regulating mitochondrial iron transport and respiration. The expansion of intronic trinucleotide repeat GAA from 8-33 repeats to >90 repeats results in Friedreich ataxia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FXN	NM_000144.5	c.483-476G>A		intron_variant		ENST00000484259.3
FXN	NM_181425.3	c.491-476G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FXN	ENST00000484259.3	c.483-476G>A		intron_variant		3	NM_000144.5	P1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75033 AN: 151954 Hom.: 18871 Cov.: 32

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.494 AC: 75097 AN: 152072 Hom.: 18888 Cov.: 32 AF XY: 0.496 AC XY: 36884 AN XY: 74362

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.645

Gnomad4 SAS AF: 0.529

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.480

Alfa AF: 0.386 Hom.: 1439

Bravo AF: 0.510

Asia WGS AF: 0.557 AC: 1939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1411675; hg19: chr9-71687052; COSMIC: COSV66009504;