chr10-93702522-ACCGCCG-A

Position:

• chr10-93702522-ACCGCCG-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000359204.5(FRA10AC1):​c.-154_-149del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0695 in 214,682 control chromosomes in the GnomAD database, including 722 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.088 (681 hom., cov: 0)
  • Exomes 𝑓: 0.029 (41 hom.)
• Consequence: FRA10AC1 ENST00000359204.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

Genes affected

FRA10AC1 (HGNC:1162): (FRA10A associated CGG repeat 1) The protein encoded by this gene is a nuclear phosphoprotein of unknown function. This gene contains a tandem CGG repeat region within a CpG island that normally consists of 8-14 repeats but can expand to over 200 repeats. The repeat region is within the 5' UTR of some transcript variants, but is intronic to another variant. The expanded repeat allele is a fragile site and becomes hypermethylated, causing a reduction in gene expression. A disease phenotype has not been associated with expanded alleles. This gene is found within the rare FRA10A folate-sensitive fragile site. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRA10AC1	NM_145246.5	c.-154_-149del		5_prime_UTR_variant	1/14	ENST00000359204.5	NP_660289.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRA10AC1	ENST00000359204.5	c.-154_-149del		5_prime_UTR_variant	1/14	1	NM_145246.5	ENSP00000360488	P1

Frequencies

GnomAD3 genomes AF: 0.0876 AC: 12901 AN: 147280 Hom.: 674 Cov.: 0

Gnomad AFR AF: 0.0700

Gnomad AMI AF: 0.0332

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0931

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.0619

Gnomad FIN AF: 0.0689

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0858

Gnomad OTH AF: 0.0942

GnomAD4 exome AF: 0.0295 AC: 1984 AN: 67284 Hom.: 41 AF XY: 0.0297 AC XY: 1246 AN XY: 41932

Gnomad4 AFR exome AF: 0.0158

Gnomad4 AMR exome AF: 0.0404

Gnomad4 ASJ exome AF: 0.0209

Gnomad4 EAS exome AF: 0.0949

Gnomad4 SAS exome AF: 0.0198

Gnomad4 FIN exome AF: 0.0250

Gnomad4 NFE exome AF: 0.0303

Gnomad4 OTH exome AF: 0.0349

GnomAD4 genome AF: 0.0878 AC: 12941 AN: 147398 Hom.: 681 Cov.: 0 AF XY: 0.0885 AC XY: 6360 AN XY: 71826

Gnomad4 AFR AF: 0.0702

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.0931

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.0620

Gnomad4 FIN AF: 0.0689

Gnomad4 NFE AF: 0.0858

Gnomad4 OTH AF: 0.0976

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs139811637; hg19: chr10-95462279;