rs12463

Positions:

• chr13-98453048-G-A

Variant summary

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

The ENST00000319562.11(FARP1):​c.*4731G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,074,126 control chromosomes in the GnomAD database, including 36,507 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 0.26 (5237 hom., cov: 33)
  • Exomes 𝑓: 0.26 (31270 hom.)
• Consequence: FARP1 ENST00000319562.11 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

Genes affected

STK24 (HGNC:11403): (serine/threonine kinase 24) This gene encodes a serine/threonine protein kinase that functions upstream of mitogen-activated protein kinase (MAPK) signaling. The encoded protein is cleaved into two chains by caspases; the N-terminal fragment (MST3/N) translocates to the nucleus and promotes programmed cells death. There is a pseudogene for this gene on chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

FARP1 (HGNC:3591): (FERM, ARH/RhoGEF and pleckstrin domain protein 1) This gene encodes a protein containing a FERM (4.2, exrin, radixin, moesin) domain, a Dbl homology domain, and two pleckstrin homology domains. These domains are found in guanine nucleotide exchange factors and proteins that link the cytoskeleton to the cell membrane. The encoded protein functions in neurons to promote dendritic growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK24	NM_001032296.4	c.*125C>T		3_prime_UTR_variant	11/11	ENST00000539966.6	NP_001027467.2
FARP1	NM_005766.4	c.*4731G>A		3_prime_UTR_variant	27/27	ENST00000319562.11	NP_005757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FARP1	ENST00000319562.11	c.*4731G>A		3_prime_UTR_variant	27/27	1	NM_005766.4	ENSP00000322926	P1
STK24	ENST00000539966.6	c.*125C>T		3_prime_UTR_variant	11/11	1	NM_001032296.4	ENSP00000442539	P1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39328 AN: 151992 Hom.: 5226 Cov.: 33

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.262

GnomAD4 exome AF: 0.257 AC: 236513 AN: 922016 Hom.: 31270 Cov.: 12 AF XY: 0.257 AC XY: 121560 AN XY: 473278

Gnomad4 AFR exome AF: 0.208

Gnomad4 AMR exome AF: 0.217

Gnomad4 ASJ exome AF: 0.256

Gnomad4 EAS exome AF: 0.141

Gnomad4 SAS exome AF: 0.225

Gnomad4 FIN exome AF: 0.245

Gnomad4 NFE exome AF: 0.270

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.259 AC: 39364 AN: 152110 Hom.: 5237 Cov.: 33 AF XY: 0.254 AC XY: 18888 AN XY: 74356

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.262

Alfa AF: 0.202 Hom.: 696

Bravo AF: 0.257

Asia WGS AF: 0.193 AC: 671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.035
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs12463; hg19: chr13-99105302;