rs1411675

Variant names:

• chr9-69072136-G-A
• rs1411675
• NM_000144.5:c.483-476G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

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]

FXN Gene-Disease associations (from GenCC):

• Friedreich ataxia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Friedreich ataxia 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Friedreich ataxia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285130 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FXN	NM_000144.5	c.483-476G>A		intron_variant	Intron 4 of 4	ENST00000484259.3	NP_000135.2
FXN	NM_181425.3	c.491-476G>A		intron_variant	Intron 4 of 4		NP_852090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FXN	ENST00000484259.3	c.483-476G>A		intron_variant	Intron 4 of 4	3	NM_000144.5	ENSP00000419243.2
ENSG00000285130	ENST00000642889.1	c.166-27765G>A		intron_variant	Intron 1 of 24			ENSP00000493780.1

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

African (AFR) AF: 0.555 AC: 23009 AN: 41480

American (AMR) AF: 0.541 AC: 8258 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1389 AN: 3470

East Asian (EAS) AF: 0.645 AC: 3333 AN: 5170

South Asian (SAS) AF: 0.529 AC: 2552 AN: 4824

European-Finnish (FIN) AF: 0.404 AC: 4272 AN: 10582

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30584 AN: 67958

Other (OTH) AF: 0.480 AC: 1013 AN: 2112

Alfa AF: 0.395 Hom.: 1576

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
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1411675; hg19: chr9-71687052; COSMIC: COSV66009504;