rs9168

Variant names:

• chr13-98449329-C-A
• rs9168
• NM_005766.4:c.*1012C>A

Variant summary

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

The NM_005766.4(FARP1):​c.*1012C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,094 control chromosomes in the GnomAD database, including 5,191 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 0.26 (5191 hom., cov: 32)
  • Exomes 𝑓: 0.21 (0 hom.)
• Consequence: FARP1 NM_005766.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FARP1	NM_005766.4	MANE Select	c.*1012C>A		3_prime_UTR	Exon 27 of 27	NP_005757.1
	STK24	NM_001032296.4	MANE Select	c.*3844G>T		3_prime_UTR	Exon 11 of 11	NP_001027467.2
	FARP1	NM_001286839.2		c.*1012C>A		3_prime_UTR	Exon 28 of 28	NP_001273768.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FARP1	ENST00000319562.11	TSL:1 MANE Select	c.*1012C>A		3_prime_UTR	Exon 27 of 27	ENSP00000322926.6
	STK24	ENST00000539966.6	TSL:1 MANE Select	c.*3844G>T		3_prime_UTR	Exon 11 of 11	ENSP00000442539.2
	FARP1	ENST00000595437.5	TSL:1	c.*1012C>A		3_prime_UTR	Exon 28 of 28	ENSP00000471242.1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39143 AN: 151962 Hom.: 5177 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.258

GnomAD4 exome AF: 0.214 AC: 3 AN: 14 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

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: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 3 AN: 12

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.258 AC: 39186 AN: 152080 Hom.: 5191 Cov.: 32 AF XY: 0.253 AC XY: 18790 AN XY: 74352

African (AFR) AF: 0.227 AC: 9394 AN: 41472

American (AMR) AF: 0.240 AC: 3674 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 890 AN: 3466

East Asian (EAS) AF: 0.154 AC: 798 AN: 5172

South Asian (SAS) AF: 0.207 AC: 993 AN: 4808

European-Finnish (FIN) AF: 0.225 AC: 2380 AN: 10584

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20157 AN: 67986

Other (OTH) AF: 0.257 AC: 543 AN: 2110

Alfa AF: 0.276 Hom.: 2713

Bravo AF: 0.255

Asia WGS AF: 0.191 AC: 664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.80
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9168; hg19: chr13-99101583;