rs584800

Positions:

• chr13-98385833-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005766.4(FARP1):​c.759+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,611,108 control chromosomes in the GnomAD database, including 31,271 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 (4424 hom., cov: 32)
  • Exomes 𝑓: 0.19 (26847 hom.)
• Consequence: FARP1 NM_005766.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.399

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FARP1	NM_005766.4	c.759+19C>T		intron_variant		ENST00000319562.11	NP_005757.1
FARP1	NM_001286839.2	c.759+19C>T		intron_variant			NP_001273768.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FARP1	ENST00000319562.11	c.759+19C>T		intron_variant		1	NM_005766.4	ENSP00000322926	P1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34878 AN: 152024 Hom.: 4409 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.221

GnomAD3 exomes AF: 0.205 AC: 51178 AN: 249376 Hom.: 5644 AF XY: 0.201 AC XY: 27144 AN XY: 134896

Gnomad AFR exome AF: 0.347

Gnomad AMR exome AF: 0.250

Gnomad ASJ exome AF: 0.173

Gnomad EAS exome AF: 0.215

Gnomad SAS exome AF: 0.224

Gnomad FIN exome AF: 0.163

Gnomad NFE exome AF: 0.176

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.187 AC: 273522 AN: 1458966 Hom.: 26847 Cov.: 31 AF XY: 0.188 AC XY: 136242 AN XY: 725610

Gnomad4 AFR exome AF: 0.355

Gnomad4 AMR exome AF: 0.243

Gnomad4 ASJ exome AF: 0.181

Gnomad4 EAS exome AF: 0.256

Gnomad4 SAS exome AF: 0.223

Gnomad4 FIN exome AF: 0.169

Gnomad4 NFE exome AF: 0.176

Gnomad4 OTH exome AF: 0.190

GnomAD4 genome AF: 0.230 AC: 34930 AN: 152142 Hom.: 4424 Cov.: 32 AF XY: 0.231 AC XY: 17152 AN XY: 74376

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.218

Alfa AF: 0.204 Hom.: 796

Bravo AF: 0.239

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.8
DANN	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs584800; hg19: chr13-99038087; COSMIC: COSV60349074; COSMIC: COSV60349074;