10-93702522-ACCGCCGCCGCCGCCGCCG-ACCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCG

Variant names:

• chr10-93702522-A-ACCGCCGCCGCCGCCG
• rs139811637
• NM_145246.5:c.-163_-149dupCGGCGGCGGCGGCGG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_145246.5(FRA10AC1):​c.-163_-149dupCGGCGGCGGCGGCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00010 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00099 (20 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.

• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.000991 (68/68614) while in subpopulation EAS AF = 0.0166 (20/1206). AF 95% confidence interval is 0.011. There are 20 homozygotes in GnomAdExome4. There are 34 alleles in the male GnomAdExome4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 20 AR gene

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.-163_-149dupCGGCGGCGGCGGCGG		5_prime_UTR	Exon 1 of 14	NP_660289.2
	FRA10AC1	NM_001347712.2		c.-364_-350dupCGGCGGCGGCGGCGG		5_prime_UTR	Exon 1 of 14	NP_001334641.1	Q70Z53-1
	FRA10AC1	NM_001347713.2		c.-283_-269dupCGGCGGCGGCGGCGG		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.-163_-149dupCGGCGGCGGCGGCGG		5_prime_UTR	Exon 1 of 14	ENSP00000360488.3	Q70Z53-1
	FRA10AC1	ENST00000959343.1		c.-163_-149dupCGGCGGCGGCGGCGG		5_prime_UTR	Exon 1 of 14	ENSP00000629402.1
	FRA10AC1	ENST00000905754.1		c.-364_-350dupCGGCGGCGGCGGCGG		5_prime_UTR	Exon 1 of 14	ENSP00000575813.1

Frequencies

GnomAD3 genomes AF: 0.000102 AC: 15 AN: 147320 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000752

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000398

Gnomad SAS AF: 0.000436

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000120

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000991 AC: 68 AN: 68614 Hom.: 20 Cov.: 0 AF XY: 0.000793 AC XY: 34 AN XY: 42852

African (AFR) AF: 0.00 AC: 0 AN: 1018

American (AMR) AF: 0.00 AC: 0 AN: 2066

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 976

East Asian (EAS) AF: 0.0166 AC: 20 AN: 1206

South Asian (SAS) AF: 0.000242 AC: 3 AN: 12402

European-Finnish (FIN) AF: 0.00179 AC: 5 AN: 2786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 228

European-Non Finnish (NFE) AF: 0.000898 AC: 40 AN: 44564

Other (OTH) AF: 0.00 AC: 0 AN: 3368

GnomAD4 genome AF: 0.000102 AC: 15 AN: 147436 Hom.: 0 Cov.: 0 AF XY: 0.0000418 AC XY: 3 AN XY: 71844

African (AFR) AF: 0.0000750 AC: 3 AN: 40006

American (AMR) AF: 0.00 AC: 0 AN: 14912

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3396

East Asian (EAS) AF: 0.000399 AC: 2 AN: 5010

South Asian (SAS) AF: 0.000436 AC: 2 AN: 4582

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.000120 AC: 8 AN: 66414

Other (OTH) AF: 0.00 AC: 0 AN: 2028

Alfa AF: 0.00 Hom.: 649

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs139811637;

hg19: chr10-95462279;