chr13-98453048-G-A

Variant names:

• chr13-98453048-G-A
• rs12463
• NM_005766.4:c.*4731G>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.*4731G>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 0.257 in 1,074,126 control chromosomes in the GnomAD database, including 36,507 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 (5237 hom., cov: 33)
  • Exomes 𝑓: 0.26 (31270 hom.)
• Consequence: FARP1 NM_005766.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• 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=-0.88).
• 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 rank	MANE	Protein	UniProt
FARP1	NM_005766.4	c.*4731G>A		3_prime_UTR_variant	Exon 27 of 27	ENST00000319562.11	NP_005757.1
STK24	NM_001032296.4	c.*125C>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000539966.6	NP_001027467.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FARP1	ENST00000319562.11	c.*4731G>A		3_prime_UTR_variant	Exon 27 of 27	1	NM_005766.4	ENSP00000322926.6
STK24	ENST00000539966.6	c.*125C>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_001032296.4	ENSP00000442539.2

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39328 AN: 151992 Hom.: 5226 Cov.: 33

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.262

GnomAD4 exome AF: 0.257 AC: 236513 AN: 922016 Hom.: 31270 Cov.: 12 AF XY: 0.257 AC XY: 121560 AN XY: 473278

African (AFR) AF: 0.208 AC: 4485 AN: 21550

American (AMR) AF: 0.217 AC: 6673 AN: 30788

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 5144 AN: 20058

East Asian (EAS) AF: 0.141 AC: 4817 AN: 34222

South Asian (SAS) AF: 0.225 AC: 14548 AN: 64590

European-Finnish (FIN) AF: 0.245 AC: 10470 AN: 42658

Middle Eastern (MID) AF: 0.204 AC: 621 AN: 3038

European-Non Finnish (NFE) AF: 0.270 AC: 179177 AN: 662752

Other (OTH) AF: 0.250 AC: 10578 AN: 42360

GnomAD4 genome AF: 0.259 AC: 39364 AN: 152110 Hom.: 5237 Cov.: 33 AF XY: 0.254 AC XY: 18888 AN XY: 74356

African (AFR) AF: 0.228 AC: 9438 AN: 41468

American (AMR) AF: 0.243 AC: 3723 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 890 AN: 3468

East Asian (EAS) AF: 0.154 AC: 796 AN: 5178

South Asian (SAS) AF: 0.212 AC: 1025 AN: 4828

European-Finnish (FIN) AF: 0.225 AC: 2385 AN: 10594

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

European-Non Finnish (NFE) AF: 0.297 AC: 20194 AN: 67962

Other (OTH) AF: 0.262 AC: 553 AN: 2114

Alfa AF: 0.243 Hom.: 1607

Bravo AF: 0.257

Asia WGS AF: 0.193 AC: 671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.035
DANN	Benign	0.68
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs12463; hg19: chr13-99105302;