chr13-98452435-T-C

Position:

• chr13-98452435-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005766.4(FARP1):​c.*4118T>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 0.226 in 152,488 control chromosomes in the GnomAD database, including 4,037 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 (4031 hom., cov: 32)
  • Exomes 𝑓: 0.18 (6 hom.)
• Consequence: FARP1 NM_005766.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.247

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK24	NM_001032296.4	c.*738A>G		3_prime_UTR_variant	11/11	ENST00000539966.6
FARP1	NM_005766.4	c.*4118T>C		3_prime_UTR_variant	27/27	ENST00000319562.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FARP1	ENST00000319562.11	c.*4118T>C		3_prime_UTR_variant	27/27	1	NM_005766.4	P1
STK24	ENST00000539966.6	c.*738A>G		3_prime_UTR_variant	11/11	1	NM_001032296.4	P1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34296 AN: 151928 Hom.: 4017 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.228

GnomAD4 exome AF: 0.176 AC: 78 AN: 442 Hom.: 6 Cov.: 0 AF XY: 0.193 AC XY: 51 AN XY: 264

Gnomad4 AFR exome AF: 1.00

Gnomad4 FIN exome AF: 0.173

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.226 AC: 34338 AN: 152046 Hom.: 4031 Cov.: 32 AF XY: 0.222 AC XY: 16491 AN XY: 74316

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.233

Alfa AF: 0.223 Hom.: 5406

Bravo AF: 0.226

Asia WGS AF: 0.212 AC: 736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	11
DANN	Benign	0.81
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: rs6956; hg19: chr13-99104689;