rs9517310

chr13-98448220-C-T

Variant summary

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

The NM_005766.4(FARP1):c.3057-16C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,607,738 control chromosomes in the GnomAD database, including 64,944 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 0.23 (4629 hom., cov: 33)
  • Exomes 𝑓: 0.28 (60315 hom.)
• Consequence: FARP1 NM_005766.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK24	NM_001032296.4	c.*4953G>A		3_prime_UTR_variant	11/11	ENST00000539966.6
FARP1	NM_005766.4	c.3057-16C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000319562.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK24	ENST00000539966.6	c.*4953G>A		3_prime_UTR_variant	11/11	1	NM_001032296.4	P1
FARP1	ENST00000319562.11	c.3057-16C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_005766.4	P1
FARP1	ENST00000595437.5	c.3150-16C>T		splice_polypyrimidine_tract_variant, intron_variant		1
FARP1	ENST00000627049.2	c.3150-16C>T		splice_polypyrimidine_tract_variant, intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35572 AN: 152054 Hom.: 4626 Cov.: 33

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.239

GnomAD3 exomes AF: 0.250 AC: 62752 AN: 251134 Hom.: 8378 AF XY: 0.254 AC XY: 34433 AN XY: 135718

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.214

Gnomad ASJ exome AF: 0.263

Gnomad EAS exome AF: 0.159

Gnomad SAS exome AF: 0.227

Gnomad FIN exome AF: 0.247

Gnomad NFE exome AF: 0.299

Gnomad OTH exome AF: 0.248

GnomAD4 exome AF: 0.283 AC: 411764 AN: 1455566 Hom.: 60315 Cov.: 29 AF XY: 0.282 AC XY: 204544 AN XY: 724462

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.214

Gnomad4 ASJ exome AF: 0.262

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.230

Gnomad4 FIN exome AF: 0.258

Gnomad4 NFE exome AF: 0.303

Gnomad4 OTH exome AF: 0.264

GnomAD4 genome AF: 0.234 AC: 35583 AN: 152172 Hom.: 4629 Cov.: 33 AF XY: 0.230 AC XY: 17108 AN XY: 74394

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.238

Alfa AF: 0.284 Hom.: 8839

Bravo AF: 0.226

Asia WGS AF: 0.184 AC: 640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.9
Dann	Benign	0.72

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: rs9517310; hg19: chr13-99100474; COSMIC: COSV60342680; COSMIC: COSV60342680;