10-93702522-ACCGCCGCCGCCGCCGCCG-ACCGCCGCCGCCGCCG

Variant names:

• chr10-93702522-ACCG-A
• rs139811637
• NM_145246.5:c.-151_-149delCGG

Variant summary

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

The NM_145246.5(FRA10AC1):​c.-151_-149delCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 213,674 control chromosomes in the GnomAD database, including 20,973 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.41 (14512 hom., cov: 0)
  • Exomes 𝑓: 0.41 (6461 hom.)
• Consequence: FRA10AC1 NM_145246.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• 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 (NFE) allele frequency at 95% confidence interval = 0.528 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.-151_-149delCGG		5_prime_UTR	Exon 1 of 14	NP_660289.2
	FRA10AC1	NM_001347712.2		c.-352_-350delCGG		5_prime_UTR	Exon 1 of 14	NP_001334641.1	Q70Z53-1
	FRA10AC1	NM_001347713.2		c.-271_-269delCGG		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.-151_-149delCGG		5_prime_UTR	Exon 1 of 14	ENSP00000360488.3	Q70Z53-1
	FRA10AC1	ENST00000959343.1		c.-151_-149delCGG		5_prime_UTR	Exon 1 of 14	ENSP00000629402.1
	FRA10AC1	ENST00000905754.1		c.-352_-350delCGG		5_prime_UTR	Exon 1 of 14	ENSP00000575813.1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 60405 AN: 147156 Hom.: 14517 Cov.: 0

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.424

GnomAD4 exome AF: 0.410 AC: 27207 AN: 66402 Hom.: 6461 AF XY: 0.415 AC XY: 17141 AN XY: 41326

African (AFR) AF: 0.0709 AC: 71 AN: 1002

American (AMR) AF: 0.311 AC: 631 AN: 2026

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 352 AN: 950

East Asian (EAS) AF: 0.310 AC: 361 AN: 1166

South Asian (SAS) AF: 0.375 AC: 4534 AN: 12088

European-Finnish (FIN) AF: 0.380 AC: 1026 AN: 2700

Middle Eastern (MID) AF: 0.388 AC: 87 AN: 224

European-Non Finnish (NFE) AF: 0.440 AC: 18902 AN: 42968

Other (OTH) AF: 0.379 AC: 1243 AN: 3278

GnomAD4 genome AF: 0.410 AC: 60403 AN: 147272 Hom.: 14512 Cov.: 0 AF XY: 0.414 AC XY: 29726 AN XY: 71754

African (AFR) AF: 0.134 AC: 5355 AN: 39982

American (AMR) AF: 0.454 AC: 6758 AN: 14890

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1674 AN: 3390

East Asian (EAS) AF: 0.388 AC: 1937 AN: 4996

South Asian (SAS) AF: 0.487 AC: 2228 AN: 4574

European-Finnish (FIN) AF: 0.573 AC: 5658 AN: 9882

Middle Eastern (MID) AF: 0.437 AC: 124 AN: 284

European-Non Finnish (NFE) AF: 0.533 AC: 35336 AN: 66346

Other (OTH) AF: 0.421 AC: 853 AN: 2026

Alfa AF: 0.328 Hom.: 649

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.0
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs139811637; hg19: chr10-95462279;