13-32007177-T-C

Variant names:

• chr13-32007177-T-C
• rs457696
• ENST00000647500.1:c.205+60996T>C

Variant summary

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

The ENST00000647500.1(FRY):​c.205+60996T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 151,622 control chromosomes in the GnomAD database, including 1,614 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 (1614 hom., cov: 32)
• Consequence: FRY ENST00000647500.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.564
• Publications: 1 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000647500.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRY	ENST00000647500.1		c.205+60996T>C		intron	N/A	ENSP00000494761.1	A0A2R8Y5V8
	FRY	ENST00000645780.1		c.-81+60996T>C		intron	N/A	ENSP00000494080.1	A0A2R8YCY2

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16344 AN: 151504 Hom.: 1610 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0943

Gnomad ASJ AF: 0.0393

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0560

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0380

Gnomad OTH AF: 0.0849

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

GnomAD4 genome AF: 0.108 AC: 16362 AN: 151622 Hom.: 1614 Cov.: 32 AF XY: 0.110 AC XY: 8123 AN XY: 74046

African (AFR) AF: 0.206 AC: 8525 AN: 41298

American (AMR) AF: 0.0944 AC: 1432 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.0393 AC: 136 AN: 3462

East Asian (EAS) AF: 0.450 AC: 2323 AN: 5160

South Asian (SAS) AF: 0.120 AC: 577 AN: 4790

European-Finnish (FIN) AF: 0.0560 AC: 588 AN: 10504

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0380 AC: 2582 AN: 67928

Other (OTH) AF: 0.0864 AC: 182 AN: 2106

Alfa AF: 0.0626 Hom.: 984

Bravo AF: 0.119

Asia WGS AF: 0.265 AC: 920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.54
PhyloP100		-0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs457696; hg19: chr13-32581314;