rs390704

Variant names:

• chr13-32064729-A-G
• rs390704
• NM_023037.3:c.71-14105A>G

Your query was ambiguous. Multiple possible variants found:

• chr13-32064729-A-G
• chr13-32064729-A-T

Variant summary

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

The NM_023037.3(FRY):​c.71-14105A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 152,098 control chromosomes in the GnomAD database, including 19,089 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 0.48 (19089 hom., cov: 32)
• Consequence: FRY NM_023037.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.947
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRY	NM_023037.3	c.71-14105A>G		intron_variant	Intron 1 of 60	ENST00000542859.6	NP_075463.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRY	ENST00000542859.6	c.71-14105A>G		intron_variant	Intron 1 of 60	5	NM_023037.3	ENSP00000445043.2

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72751 AN: 151980 Hom.: 19075 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.479 AC: 72786 AN: 152098 Hom.: 19089 Cov.: 32 AF XY: 0.480 AC XY: 35699 AN XY: 74350

African (AFR) AF: 0.259 AC: 10748 AN: 41502

American (AMR) AF: 0.574 AC: 8769 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2145 AN: 3464

East Asian (EAS) AF: 0.347 AC: 1800 AN: 5184

South Asian (SAS) AF: 0.573 AC: 2762 AN: 4818

European-Finnish (FIN) AF: 0.539 AC: 5701 AN: 10580

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39118 AN: 67966

Other (OTH) AF: 0.508 AC: 1071 AN: 2108

Alfa AF: 0.545 Hom.: 89951

Bravo AF: 0.467

Asia WGS AF: 0.454 AC: 1579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.70
PhyloP100		0.95
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: rs390704; hg19: chr13-32638866; COSMIC: COSV66578283;