rs10521869

Positions:

• chrX-148012775-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000370467.8(FMR1NB):​c.632+4064T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 111,120 control chromosomes in the GnomAD database, including 1,858 homozygotes. There are 5,011 hemizygotes in GnomAD. 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 0.17 (1858 hom., 5011 hem., cov: 22)
• Consequence: FMR1NB ENST00000370467.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.554

Genes affected

FMR1NB (HGNC:26372): (FMR1 neighbor) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FMR1NB	NM_152578.3	c.632+4064T>C		intron_variant		ENST00000370467.8	NP_689791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FMR1NB	ENST00000370467.8	c.632+4064T>C		intron_variant		1	NM_152578.3	ENSP00000359498	P1
FMR1NB	ENST00000489034.2	c.121+4064T>C		intron_variant, NMD_transcript_variant		3		ENSP00000435769

Frequencies

GnomAD3 genomes AF: 0.166 AC: 18483 AN: 111073 Hom.: 1859 Cov.: 22 AF XY: 0.150 AC XY: 4996 AN XY: 33339

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.0596

Gnomad AMR AF: 0.0882

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.00140

Gnomad SAS AF: 0.0703

Gnomad FIN AF: 0.0410

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.166 AC: 18491 AN: 111120 Hom.: 1858 Cov.: 22 AF XY: 0.150 AC XY: 5011 AN XY: 33396

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.0880

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.00140

Gnomad4 SAS AF: 0.0694

Gnomad4 FIN AF: 0.0410

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.163

Alfa AF: 0.165 Hom.: 961

Bravo AF: 0.180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	16
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs10521869; hg19: chrX-147094295;