10-93677717-A-G

Variant names:

• chr10-93677717-A-G
• rs10786122
• NM_145246.5:c.788-1026T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145246.5(FRA10AC1):​c.788-1026T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 152,072 control chromosomes in the GnomAD database, including 34,265 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (34265 hom., cov: 32)
• Consequence: FRA10AC1 NM_145246.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.564
• Publications: 2 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: G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.729 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRA10AC1	NM_145246.5	MANE Select	c.788-1026T>C		intron	N/A	NP_660289.2
	FRA10AC1	NM_001347712.2		c.788-1026T>C		intron	N/A	NP_001334641.1
	FRA10AC1	NM_001347713.2		c.788-1026T>C		intron	N/A	NP_001334642.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRA10AC1	ENST00000359204.5	TSL:1 MANE Select	c.788-1026T>C		intron	N/A	ENSP00000360488.3

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100894 AN: 151952 Hom.: 34248 Cov.: 32

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.777

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.685

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.664 AC: 100953 AN: 152072 Hom.: 34265 Cov.: 32 AF XY: 0.662 AC XY: 49177 AN XY: 74332

African (AFR) AF: 0.512 AC: 21253 AN: 41474

American (AMR) AF: 0.685 AC: 10457 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2829 AN: 3470

East Asian (EAS) AF: 0.700 AC: 3603 AN: 5150

South Asian (SAS) AF: 0.627 AC: 3020 AN: 4820

European-Finnish (FIN) AF: 0.712 AC: 7523 AN: 10566

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.734 AC: 49937 AN: 67996

Other (OTH) AF: 0.684 AC: 1445 AN: 2114

Alfa AF: 0.677 Hom.: 4550

Bravo AF: 0.661

Asia WGS AF: 0.659 AC: 2292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	8.0
DANN	Benign	0.59
PhyloP100		0.56
Mutation Taster		=100/0	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: rs10786122; hg19: chr10-95437474;