chr17-7607969-T-C

Variant names:

• chr17-7607969-T-C
• rs858524
• NM_004860.4:c.82-1820A>G

Variant summary

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

The NM_004860.4(FXR2):​c.82-1820A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 151,624 control chromosomes in the GnomAD database, including 17,481 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 0.46 (17481 hom., cov: 30)
• Consequence: FXR2 NM_004860.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277
• Publications: 10 publications found

Genes affected

FXR2 (HGNC:4024): (FMR1 autosomal homolog 2) The protein encoded by this gene is a RNA binding protein containing two KH domains and one RCG box, which is similar to FMRP and FXR1. It associates with polyribosomes, predominantly with 60S large ribosomal subunits. This encoded protein may self-associate or interact with FMRP and FXR1. It may have a role in the development of fragile X cognitive disability syndrome. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004860.4. 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
	FXR2	NM_004860.4	MANE Select	c.82-1820A>G		intron	N/A	NP_004851.2	P51116

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXR2	ENST00000250113.12	TSL:1 MANE Select	c.82-1820A>G		intron	N/A	ENSP00000250113.7	P51116
	FXR2	ENST00000704984.1		c.301-1820A>G		intron	N/A	ENSP00000516064.1	A0A994J7P9
	FXR2	ENST00000571597.1	TSL:4	c.-129-1820A>G		intron	N/A	ENSP00000459230.1	I3L1Z2

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69342 AN: 151508 Hom.: 17483 Cov.: 30

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.457 AC: 69358 AN: 151624 Hom.: 17481 Cov.: 30 AF XY: 0.457 AC XY: 33851 AN XY: 74054

African (AFR) AF: 0.237 AC: 9789 AN: 41328

American (AMR) AF: 0.419 AC: 6371 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2244 AN: 3464

East Asian (EAS) AF: 0.429 AC: 2207 AN: 5144

South Asian (SAS) AF: 0.637 AC: 3068 AN: 4814

European-Finnish (FIN) AF: 0.488 AC: 5108 AN: 10466

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38871 AN: 67884

Other (OTH) AF: 0.485 AC: 1021 AN: 2104

Alfa AF: 0.479 Hom.: 2327

Bravo AF: 0.439

Asia WGS AF: 0.502 AC: 1746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.4
DANN	Benign	0.36
PhyloP100		0.28
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: rs858524; hg19: chr17-7511287;