rs9168

Positions:

• chr13-98449329-C-A

Variant summary

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

The NM_005766.4(FARP1):​c.*1012C>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 0.258 in 152,094 control chromosomes in the GnomAD database, including 5,191 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 (5191 hom., cov: 32)
  • Exomes 𝑓: 0.21 (0 hom.)
• Consequence: FARP1 NM_005766.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK24	NM_001032296.4	c.*3844G>T		3_prime_UTR_variant	11/11	ENST00000539966.6
FARP1	NM_005766.4	c.*1012C>A		3_prime_UTR_variant	27/27	ENST00000319562.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FARP1	ENST00000319562.11	c.*1012C>A		3_prime_UTR_variant	27/27	1	NM_005766.4	P1
STK24	ENST00000539966.6	c.*3844G>T		3_prime_UTR_variant	11/11	1	NM_001032296.4	P1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39143 AN: 151962 Hom.: 5177 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.258

GnomAD4 exome AF: 0.214 AC: 3 AN: 14 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.258 AC: 39186 AN: 152080 Hom.: 5191 Cov.: 32 AF XY: 0.253 AC XY: 18790 AN XY: 74352

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.257

Alfa AF: 0.278 Hom.: 2332

Bravo AF: 0.255

Asia WGS AF: 0.191 AC: 664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9168; hg19: chr13-99101583;