rs1800652

Positions:

• chr9-69046200-G-A
• chr9-69046200-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000144.5(FXN):​c.166-185G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,104 control chromosomes in the GnomAD database, including 4,690 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.24 (4690 hom., cov: 32)
• Consequence: FXN NM_000144.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.239

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]

ENSG00000285130 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 9-69046200-G-A is Benign according to our data. Variant chr9-69046200-G-A is described in ClinVar as [Benign]. Clinvar id is 1293281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FXN	NM_000144.5	c.166-185G>A		intron_variant		ENST00000484259.3	NP_000135.2
FXN	NM_181425.3	c.166-185G>A		intron_variant			NP_852090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FXN	ENST00000484259.3	c.166-185G>A		intron_variant		3	NM_000144.5	ENSP00000419243.2
ENSG00000285130	ENST00000642889.1	c.165+10253G>A		intron_variant				ENSP00000493780.1

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37110 AN: 151986 Hom.: 4695 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.244 AC: 37118 AN: 152104 Hom.: 4690 Cov.: 32 AF XY: 0.241 AC XY: 17887 AN XY: 74350

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.275

Alfa AF: 0.252 Hom.: 602

Bravo AF: 0.245

Asia WGS AF: 0.298 AC: 1037 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.38

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: rs1800652; hg19: chr9-71661116;