rs673069

Positions:

• chr13-98393739-A-G

Variant summary

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

The NM_005766.4(FARP1):​c.1164+21A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00758 in 1,592,968 control chromosomes in the GnomAD database, including 680 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 0.038 (374 hom., cov: 33)
  • Exomes 𝑓: 0.0043 (306 hom.)
• Consequence: FARP1 NM_005766.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.57

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FARP1	NM_005766.4	c.1164+21A>G		intron_variant		ENST00000319562.11
FARP1	NM_001286839.2	c.1164+21A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FARP1	ENST00000319562.11	c.1164+21A>G		intron_variant		1	NM_005766.4	P1

Frequencies

GnomAD3 genomes AF: 0.0382 AC: 5808 AN: 152162 Hom.: 373 Cov.: 33

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0198

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000735

Gnomad OTH AF: 0.0244

GnomAD3 exomes AF: 0.0114 AC: 2844 AN: 248930 Hom.: 156 AF XY: 0.00893 AC XY: 1200 AN XY: 134406

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.00629

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0204

Gnomad SAS exome AF: 0.000803

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.000382

Gnomad OTH exome AF: 0.00442

GnomAD4 exome AF: 0.00435 AC: 6262 AN: 1440688 Hom.: 306 Cov.: 26 AF XY: 0.00386 AC XY: 2773 AN XY: 717772

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.00678

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0197

Gnomad4 SAS exome AF: 0.000878

Gnomad4 FIN exome AF: 0.0000937

Gnomad4 NFE exome AF: 0.000175

Gnomad4 OTH exome AF: 0.00851

GnomAD4 genome AF: 0.0382 AC: 5819 AN: 152280 Hom.: 374 Cov.: 33 AF XY: 0.0380 AC XY: 2833 AN XY: 74466

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.0131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0199

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000735

Gnomad4 OTH AF: 0.0255

Alfa AF: 0.0350 Hom.: 61

Bravo AF: 0.0421

Asia WGS AF: 0.0110 AC: 41 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.015
DANN	Benign	0.18
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: rs673069; hg19: chr13-99045993;