13-98390136-T-C

Position:

• chr13-98390136-T-C

Variant summary

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

The ENST00000319562.11(FARP1):​c.1019+16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,609,740 control chromosomes in the GnomAD database, including 38,571 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 0.29 (8392 hom., cov: 32)
  • Exomes 𝑓: 0.19 (30179 hom.)
• Consequence: FARP1 ENST00000319562.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FARP1	NM_005766.4	c.1019+16T>C		intron_variant		ENST00000319562.11	NP_005757.1
FARP1	NM_001286839.2	c.1019+16T>C		intron_variant			NP_001273768.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FARP1	ENST00000319562.11	c.1019+16T>C		intron_variant		1	NM_005766.4	ENSP00000322926	P1
FARP1	ENST00000595437.5	c.1019+16T>C		intron_variant		1		ENSP00000471242
FARP1	ENST00000596580.2	c.1019+16T>C		intron_variant		5		ENSP00000490391
FARP1	ENST00000627049.2	c.1019+16T>C		intron_variant		5		ENSP00000486285

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43736 AN: 151996 Hom.: 8365 Cov.: 32

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.259

GnomAD3 exomes AF: 0.224 AC: 55629 AN: 248758 Hom.: 7473 AF XY: 0.216 AC XY: 28986 AN XY: 134406

Gnomad AFR exome AF: 0.558

Gnomad AMR exome AF: 0.265

Gnomad ASJ exome AF: 0.179

Gnomad EAS exome AF: 0.238

Gnomad SAS exome AF: 0.233

Gnomad FIN exome AF: 0.166

Gnomad NFE exome AF: 0.174

Gnomad OTH exome AF: 0.201

GnomAD4 exome AF: 0.192 AC: 279720 AN: 1457626 Hom.: 30179 Cov.: 32 AF XY: 0.192 AC XY: 139022 AN XY: 724750

Gnomad4 AFR exome AF: 0.562

Gnomad4 AMR exome AF: 0.259

Gnomad4 ASJ exome AF: 0.186

Gnomad4 EAS exome AF: 0.282

Gnomad4 SAS exome AF: 0.230

Gnomad4 FIN exome AF: 0.171

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.288 AC: 43814 AN: 152114 Hom.: 8392 Cov.: 32 AF XY: 0.287 AC XY: 21375 AN XY: 74376

Gnomad4 AFR AF: 0.550

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.257

Alfa AF: 0.254 Hom.: 1442

Bravo AF: 0.305

Asia WGS AF: 0.276 AC: 961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.2
DANN	Benign	0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2256823; hg19: chr13-99042390; COSMIC: COSV60330358; COSMIC: COSV60330358;