NM_145246.5:c.787+951T>C

Variant names:

• chr10-93680529-A-G
• rs10509663
• NM_145246.5:c.787+951T>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.787+951T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,192 control chromosomes in the GnomAD database, including 1,422 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 0.11 (1422 hom., cov: 32)
• Consequence: FRA10AC1 NM_145246.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRA10AC1	NM_145246.5	c.787+951T>C		intron_variant	Intron 11 of 13	ENST00000359204.5	NP_660289.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRA10AC1	ENST00000359204.5	c.787+951T>C		intron_variant	Intron 11 of 13	1	NM_145246.5	ENSP00000360488.3

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16563 AN: 152074 Hom.: 1416 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.0526

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0546

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0514

Gnomad OTH AF: 0.0881

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

GnomAD4 genome AF: 0.109 AC: 16586 AN: 152192 Hom.: 1422 Cov.: 32 AF XY: 0.109 AC XY: 8134 AN XY: 74422

African (AFR) AF: 0.223 AC: 9252 AN: 41492

American (AMR) AF: 0.0526 AC: 804 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0282 AC: 98 AN: 3470

East Asian (EAS) AF: 0.231 AC: 1195 AN: 5170

South Asian (SAS) AF: 0.168 AC: 812 AN: 4828

European-Finnish (FIN) AF: 0.0546 AC: 580 AN: 10614

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0514 AC: 3495 AN: 68010

Other (OTH) AF: 0.0924 AC: 195 AN: 2110

Alfa AF: 0.0763 Hom.: 1421

Bravo AF: 0.112

Asia WGS AF: 0.200 AC: 695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.66
PhyloP100		0.062
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: rs10509663; hg19: chr10-95440286;