rs7988959

Positions:

• chr13-98451750-T-C

Variant summary

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

The NM_005766.4(FARP1):​c.*3433T>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 0.23 in 152,156 control chromosomes in the GnomAD database, including 4,433 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 (4433 hom., cov: 32)
  • Exomes 𝑓: 0.22 (0 hom.)
• Consequence: FARP1 NM_005766.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.89

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=-0.9).
• 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.*1423A>G		3_prime_UTR_variant	11/11	ENST00000539966.6	NP_001027467.2
FARP1	NM_005766.4	c.*3433T>C		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.*3433T>C		3_prime_UTR_variant	27/27	1	NM_005766.4	ENSP00000322926	P1
STK24	ENST00000539966.6	c.*1423A>G		3_prime_UTR_variant	11/11	1	NM_001032296.4	ENSP00000442539	P1
STK24	ENST00000376554.8	c.*1423A>G		3_prime_UTR_variant	5/5	5		ENSP00000365737
STK24	ENST00000397517.6	c.*1423A>G		3_prime_UTR_variant	10/10	2		ENSP00000380651

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34909 AN: 152006 Hom.: 4431 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.219 AC: 7 AN: 32 Hom.: 0 Cov.: 0 AF XY: 0.182 AC XY: 4 AN XY: 22

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.273

GnomAD4 genome AF: 0.230 AC: 34917 AN: 152124 Hom.: 4433 Cov.: 32 AF XY: 0.225 AC XY: 16758 AN XY: 74358

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.232

Alfa AF: 0.272 Hom.: 5890

Bravo AF: 0.223

Asia WGS AF: 0.185 AC: 644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.47

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: rs7988959; hg19: chr13-99104004;