10-93702522-ACCGCCGCCGCCGCCGCCG-ACCGCCGCCGCCG

Variant names:

• chr10-93702522-ACCGCCG-A
• rs139811637
• NM_145246.5:c.-154_-149delCGGCGG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_145246.5(FRA10AC1):​c.-154_-149delCGGCGG 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 NM_145246.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 1 publications found

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]

FRA10AC1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalities

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145246.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRA10AC1	NM_145246.5	MANE Select	c.-154_-149delCGGCGG		5_prime_UTR	Exon 1 of 14	NP_660289.2
	FRA10AC1	NM_001347712.2		c.-355_-350delCGGCGG		5_prime_UTR	Exon 1 of 14	NP_001334641.1	Q70Z53-1
	FRA10AC1	NM_001347713.2		c.-274_-269delCGGCGG		5_prime_UTR	Exon 1 of 15	NP_001334642.1	Q70Z53-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRA10AC1	ENST00000359204.5	TSL:1 MANE Select	c.-154_-149delCGGCGG		5_prime_UTR	Exon 1 of 14	ENSP00000360488.3	Q70Z53-1
	FRA10AC1	ENST00000959343.1		c.-154_-149delCGGCGG		5_prime_UTR	Exon 1 of 14	ENSP00000629402.1
	FRA10AC1	ENST00000905754.1		c.-355_-350delCGGCGG		5_prime_UTR	Exon 1 of 14	ENSP00000575813.1

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0158 AC: 16 AN: 1012

American (AMR) AF: 0.0404 AC: 83 AN: 2056

Ashkenazi Jewish (ASJ) AF: 0.0209 AC: 20 AN: 958

East Asian (EAS) AF: 0.0949 AC: 108 AN: 1138

South Asian (SAS) AF: 0.0198 AC: 244 AN: 12294

European-Finnish (FIN) AF: 0.0250 AC: 69 AN: 2758

Middle Eastern (MID) AF: 0.0364 AC: 8 AN: 220

European-Non Finnish (NFE) AF: 0.0303 AC: 1321 AN: 43550

Other (OTH) AF: 0.0349 AC: 115 AN: 3298

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.0702 AC: 2807 AN: 39994

American (AMR) AF: 0.102 AC: 1528 AN: 14910

Ashkenazi Jewish (ASJ) AF: 0.0931 AC: 316 AN: 3396

East Asian (EAS) AF: 0.270 AC: 1353 AN: 5008

South Asian (SAS) AF: 0.0620 AC: 284 AN: 4582

European-Finnish (FIN) AF: 0.0689 AC: 682 AN: 9894

Middle Eastern (MID) AF: 0.155 AC: 44 AN: 284

European-Non Finnish (NFE) AF: 0.0858 AC: 5699 AN: 66398

Other (OTH) AF: 0.0976 AC: 198 AN: 2028

Alfa AF: 0.0442 Hom.: 649

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=299/1	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs139811637; hg19: chr10-95462279;