13-98450223-GCC-GC

Position:

• chr13-98450223-GCC-GC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_005766.4(FARP1):​c.*1910del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,062 control chromosomes in the GnomAD database, including 5,160 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (5160 hom., cov: 21)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FARP1 NM_005766.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.525

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 -8 ACMG points.

• 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.*2949del		3_prime_UTR_variant	11/11	ENST00000539966.6
FARP1	NM_005766.4	c.*1910del		3_prime_UTR_variant	27/27	ENST00000319562.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FARP1	ENST00000319562.11	c.*1910del		3_prime_UTR_variant	27/27	1	NM_005766.4	P1
STK24	ENST00000539966.6	c.*2949del		3_prime_UTR_variant	11/11	1	NM_001032296.4	P1
STK24	ENST00000376554.8	c.*2949del		3_prime_UTR_variant	5/5	5
STK24	ENST00000397517.6	c.*2949del		3_prime_UTR_variant	10/10	2

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39007 AN: 151944 Hom.: 5150 Cov.: 21

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.256

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.257 AC: 39040 AN: 152062 Hom.: 5160 Cov.: 21 AF XY: 0.252 AC XY: 18728 AN XY: 74316

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.255

Alfa AF: 0.286 Hom.: 794

Bravo AF: 0.254

Asia WGS AF: 0.190 AC: 663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs3832885; hg19: chr13-99102477;