rs4584

Positions:

• chr13-98449615-G-C

Variant summary

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

The NM_005766.4(FARP1):​c.*1298G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,470 control chromosomes in the GnomAD database, including 5,746 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 0.27 (5729 hom., cov: 31)
  • Exomes 𝑓: 0.26 (17 hom.)
• Consequence: FARP1 NM_005766.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

Genes affected

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]

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FARP1	NM_005766.4	c.*1298G>C		3_prime_UTR_variant	27/27	ENST00000319562.11	NP_005757.1
STK24	NM_001032296.4	c.*3558C>G		3_prime_UTR_variant	11/11	ENST00000539966.6	NP_001027467.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FARP1	ENST00000319562.11	c.*1298G>C		3_prime_UTR_variant	27/27	1	NM_005766.4	ENSP00000322926.6
STK24	ENST00000539966	c.*3558C>G		3_prime_UTR_variant	11/11	1	NM_001032296.4	ENSP00000442539.2

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41223 AN: 151864 Hom.: 5714 Cov.: 31

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.266

GnomAD4 exome AF: 0.256 AC: 125 AN: 488 Hom.: 17 Cov.: 0 AF XY: 0.273 AC XY: 84 AN XY: 308

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.500

Gnomad4 FIN exome AF: 0.244

Gnomad4 NFE exome AF: 0.368

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.272 AC: 41279 AN: 151982 Hom.: 5729 Cov.: 31 AF XY: 0.267 AC XY: 19862 AN XY: 74284

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.266

Alfa AF: 0.298 Hom.: 921

Bravo AF: 0.270

Asia WGS AF: 0.214 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.85
DANN	Benign	0.48

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: rs4584; hg19: chr13-99101869; COSMIC: COSV60351723; COSMIC: COSV60351723;