10-93702522-ACCGCCGCCGCCGCCGCCG-ACCGCCGCCGCCGCCGCCGCCGCCGCCG

Variant names:

• chr10-93702522-A-ACCGCCGCCG
• rs139811637
• NM_145246.5:c.-157_-149dupCGGCGGCGG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_145246.5(FRA10AC1):​c.-157_-149dupCGGCGGCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00056 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0014 (9 hom.)
• Consequence: FRA10AC1 NM_145246.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000556 (82/147430) while in subpopulation SAS AF= 0.00371 (17/4582). AF 95% confidence interval is 0.00236. There are 0 homozygotes in gnomad4. There are 49 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRA10AC1	NM_145246.5	c.-157_-149dupCGGCGGCGG		5_prime_UTR_variant	Exon 1 of 14	ENST00000359204.5	NP_660289.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRA10AC1	ENST00000359204.5	c.-157_-149dupCGGCGGCGG		5_prime_UTR_variant	Exon 1 of 14	1	NM_145246.5	ENSP00000360488.3

Frequencies

GnomAD3 genomes AF: 0.000550 AC: 81 AN: 147314 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000672

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000597

Gnomad SAS AF: 0.00392

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000135

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00141 AC: 97 AN: 68608 Hom.: 9 Cov.: 0 AF XY: 0.00177 AC XY: 76 AN XY: 42846

Gnomad4 AFR exome AF: 0.000982

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00637

Gnomad4 FIN exome AF: 0.000359

Gnomad4 NFE exome AF: 0.000292

Gnomad4 OTH exome AF: 0.000891

GnomAD4 genome AF: 0.000556 AC: 82 AN: 147430 Hom.: 0 Cov.: 0 AF XY: 0.000682 AC XY: 49 AN XY: 71838

Gnomad4 AFR AF: 0.00130

Gnomad4 AMR AF: 0.0000671

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000599

Gnomad4 SAS AF: 0.00371

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000136

Gnomad4 OTH AF: 0.00

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;