11-126269114-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000692336.1(FOXRED1):c.-93C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000829 in 1,103,734 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00038 (3 hom.)
• Consequence: FOXRED1 ENST00000692336.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0790

Genes affected

FOXRED1 (HGNC:26927): (FAD dependent oxidoreductase domain containing 1) This gene encodes a protein that contains a FAD-dependent oxidoreductase domain. The encoded protein is localized to the mitochondria and may function as a chaperone protein required for the function of mitochondrial complex I. Mutations in this gene are associated with mitochondrial complex I deficiency. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2010]

SRPRA (HGNC:11307): (SRP receptor subunit alpha) The gene encodes a subunit of the endoplasmic reticulum signal recognition particle receptor that, in conjunction with the signal recognition particle, is involved in the targeting and translocation of signal sequence tagged secretory and membrane proteins across the endoplasmic reticulum. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 11-126269114-C-G is Benign according to our data. Variant chr11-126269114-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1199467.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00362 (552/152356) while in subpopulation AFR AF= 0.0127 (530/41590). AF 95% confidence interval is 0.0118. There are 4 homozygotes in gnomad4. There are 248 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXRED1	NM_017547.4			upstream_gene_variant		ENST00000263578.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXRED1	ENST00000263578.10			upstream_gene_variant		1	NM_017547.4	P3

Frequencies

GnomAD3 genomes AF: 0.00363 AC: 552 AN: 152238 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000861 AC: 183 AN: 212556 Hom.: 0 AF XY: 0.000648 AC XY: 75 AN XY: 115734

Gnomad AFR exome AF: 0.0138

Gnomad AMR exome AF: 0.0000992

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000349

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000365

GnomAD4 exome AF: 0.000382 AC: 363 AN: 951378 Hom.: 3 Cov.: 13 AF XY: 0.000327 AC XY: 161 AN XY: 492590

Gnomad4 AFR exome AF: 0.0130

Gnomad4 AMR exome AF: 0.000422

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000134

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000152

Gnomad4 OTH exome AF: 0.000598

GnomAD4 genome AF: 0.00362 AC: 552 AN: 152356 Hom.: 4 Cov.: 33 AF XY: 0.00333 AC XY: 248 AN XY: 74500

Gnomad4 AFR AF: 0.0127

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00167 Hom.: 0

Bravo AF: 0.00398

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	15
Dann	Benign	0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs139053088; hg19: chr11-126139009;