rs1334891

Positions:

• chr10-97321114-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005479.4(FRAT1):​c.*821G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 167,120 control chromosomes in the GnomAD database, including 6,053 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 0.25 (5612 hom., cov: 32)
  • Exomes 𝑓: 0.25 (441 hom.)
• Consequence: FRAT1 NM_005479.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630

Genes affected

FRAT1 (HGNC:3944): (FRAT regulator of WNT signaling pathway 1) The protein encoded by this gene belongs to the GSK-3-binding protein family. The protein inhibits GSK-3-mediated phosphorylation of beta-catenin and positively regulates the Wnt signaling pathway. It may function in tumor progression and in lymphomagenesis. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRAT1	NM_005479.4	c.*821G>T		3_prime_UTR_variant	1/1	ENST00000371021.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRAT1	ENST00000371021.5	c.*821G>T		3_prime_UTR_variant	1/1		NM_005479.4	P1
FRAT1	ENST00000490980.1	n.374G>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37590 AN: 152054 Hom.: 5621 Cov.: 32

Gnomad AFR AF: 0.0700

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.294

GnomAD4 exome AF: 0.246 AC: 3672 AN: 14948 Hom.: 441 Cov.: 0 AF XY: 0.245 AC XY: 1744 AN XY: 7118

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.245

Gnomad4 NFE exome AF: 0.279

Gnomad4 OTH exome AF: 0.350

GnomAD4 genome AF: 0.247 AC: 37579 AN: 152172 Hom.: 5612 Cov.: 32 AF XY: 0.246 AC XY: 18270 AN XY: 74400

Gnomad4 AFR AF: 0.0698

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.294

Alfa AF: 0.308 Hom.: 8523

Bravo AF: 0.248

Asia WGS AF: 0.284 AC: 987 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.78

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: rs1334891; hg19: chr10-99080871; COSMIC: COSV64017486;