13-32285286-C-G

Variant names:

• chr13-32285286-C-G
• rs114827
• NM_023037.3:c.8470-4347C>G

Variant summary

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

The NM_023037.3(FRY):​c.8470-4347C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 151,988 control chromosomes in the GnomAD database, including 4,156 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 0.21 (4156 hom., cov: 32)
• Consequence: FRY NM_023037.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260
• Publications: 0 publications found

Genes affected

FRY (HGNC:20367): (FRY microtubule binding protein) Predicted to enable enzyme inhibitor activity. Predicted to be involved in cell morphogenesis and neuron projection development. Predicted to be located in microtubule organizing center and spindle pole. Predicted to be active in cell cortex and site of polarized growth. [provided by Alliance of Genome Resources, Apr 2022]

FRY Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023037.3. 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
	FRY	NM_023037.3	MANE Select	c.8470-4347C>G		intron	N/A	NP_075463.2	Q5TBA9
	FRY	NM_001411012.1		c.8479-4347C>G		intron	N/A	NP_001397941.1	A0A286YFA9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRY	ENST00000542859.6	TSL:5 MANE Select	c.8470-4347C>G		intron	N/A	ENSP00000445043.2	Q5TBA9
	FRY	ENST00000647500.1		c.8605-4347C>G		intron	N/A	ENSP00000494761.1	A0A2R8Y5V8
	FRY	ENST00000642040.1		c.8479-4347C>G		intron	N/A	ENSP00000493189.1	A0A286YFA9

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31659 AN: 151870 Hom.: 4160 Cov.: 32

Gnomad AFR AF: 0.0543

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.0399

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.208 AC: 31649 AN: 151988 Hom.: 4156 Cov.: 32 AF XY: 0.207 AC XY: 15365 AN XY: 74310

African (AFR) AF: 0.0541 AC: 2244 AN: 41444

American (AMR) AF: 0.248 AC: 3789 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 798 AN: 3470

East Asian (EAS) AF: 0.0398 AC: 206 AN: 5182

South Asian (SAS) AF: 0.211 AC: 1017 AN: 4812

European-Finnish (FIN) AF: 0.261 AC: 2755 AN: 10556

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19980 AN: 67944

Other (OTH) AF: 0.230 AC: 485 AN: 2108

Alfa AF: 0.122 Hom.: 226

Bravo AF: 0.202

Asia WGS AF: 0.115 AC: 400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.69
PhyloP100		-0.26
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: rs114827; hg19: chr13-32859423;