rs4584

Variant names:

• chr13-98449615-G-C
• rs4584
• NM_005766.4:c.*1298G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005766.4(FARP1):​c.*1298G>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 0.272 in 152,470 control chromosomes in the GnomAD database, including 5,746 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 0.27 (5729 hom., cov: 31)
  • Exomes 𝑓: 0.26 (17 hom.)
• Consequence: FARP1 NM_005766.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 9 publications found

Genes affected

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]

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005766.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FARP1	NM_005766.4	MANE Select	c.*1298G>C		3_prime_UTR	Exon 27 of 27	NP_005757.1	A0A2X0TVY0
	STK24	NM_001032296.4	MANE Select	c.*3558C>G		3_prime_UTR	Exon 11 of 11	NP_001027467.2	Q9Y6E0-2
	FARP1	NM_001286839.2		c.*1298G>C		3_prime_UTR	Exon 28 of 28	NP_001273768.1	C9JME2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FARP1	ENST00000319562.11	TSL:1 MANE Select	c.*1298G>C		3_prime_UTR	Exon 27 of 27	ENSP00000322926.6	Q9Y4F1-1
	STK24	ENST00000539966.6	TSL:1 MANE Select	c.*3558C>G		3_prime_UTR	Exon 11 of 11	ENSP00000442539.2	Q9Y6E0-2
	FARP1	ENST00000595437.5	TSL:1	c.*1298G>C		3_prime_UTR	Exon 28 of 28	ENSP00000471242.1	C9JME2

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41223 AN: 151864 Hom.: 5714 Cov.: 31

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.266

GnomAD4 exome AF: 0.256 AC: 125 AN: 488 Hom.: 17 Cov.: 0 AF XY: 0.273 AC XY: 84 AN XY: 308

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.244 AC: 106 AN: 434

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.368 AC: 14 AN: 38

Other (OTH) AF: 0.300 AC: 3 AN: 10

GnomAD4 genome AF: 0.272 AC: 41279 AN: 151982 Hom.: 5729 Cov.: 31 AF XY: 0.267 AC XY: 19862 AN XY: 74284

African (AFR) AF: 0.267 AC: 11070 AN: 41440

American (AMR) AF: 0.244 AC: 3731 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 907 AN: 3470

East Asian (EAS) AF: 0.169 AC: 873 AN: 5164

South Asian (SAS) AF: 0.230 AC: 1103 AN: 4804

European-Finnish (FIN) AF: 0.225 AC: 2374 AN: 10556

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.299 AC: 20300 AN: 67964

Other (OTH) AF: 0.266 AC: 562 AN: 2112

Alfa AF: 0.298 Hom.: 921

Bravo AF: 0.270

Asia WGS AF: 0.214 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.85
DANN	Benign	0.48
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4584; hg19: chr13-99101869; COSMIC: COSV60351723; COSMIC: COSV60351723;