rs2291175

Positions:

• chr13-98410724-G-T

Variant summary

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

The NM_005766.4(FARP1):​c.1603-10G>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0392 in 1,515,532 control chromosomes in the GnomAD database, including 1,526 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 0.033 (140 hom., cov: 33)
  • Exomes 𝑓: 0.040 (1386 hom.)
• Consequence: FARP1 NM_005766.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0004121
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313

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=-0.72).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FARP1	NM_005766.4	c.1603-10G>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000319562.11
FARP1	NM_001286839.2	c.1603-10G>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FARP1	ENST00000319562.11	c.1603-10G>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_005766.4	P1
FARP1	ENST00000595437.5	c.1603-10G>T		splice_polypyrimidine_tract_variant, intron_variant		1
FARP1	ENST00000627049.2	c.1603-10G>T		splice_polypyrimidine_tract_variant, intron_variant		5
FARP1	ENST00000457029.3	n.241-10G>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0328 AC: 4984 AN: 152076 Hom.: 133 Cov.: 33

Gnomad AFR AF: 0.00674

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0190

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.0718

Gnomad SAS AF: 0.0840

Gnomad FIN AF: 0.0630

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0396

Gnomad OTH AF: 0.0354

GnomAD3 exomes AF: 0.0466 AC: 10832 AN: 232450 Hom.: 350 AF XY: 0.0497 AC XY: 6211 AN XY: 125080

Gnomad AFR exome AF: 0.00589

Gnomad AMR exome AF: 0.0163

Gnomad ASJ exome AF: 0.0559

Gnomad EAS exome AF: 0.0748

Gnomad SAS exome AF: 0.0865

Gnomad FIN exome AF: 0.0632

Gnomad NFE exome AF: 0.0422

Gnomad OTH exome AF: 0.0460

GnomAD4 exome AF: 0.0399 AC: 54430 AN: 1363338 Hom.: 1386 Cov.: 20 AF XY: 0.0416 AC XY: 28304 AN XY: 679954

Gnomad4 AFR exome AF: 0.00617

Gnomad4 AMR exome AF: 0.0168

Gnomad4 ASJ exome AF: 0.0558

Gnomad4 EAS exome AF: 0.0580

Gnomad4 SAS exome AF: 0.0838

Gnomad4 FIN exome AF: 0.0603

Gnomad4 NFE exome AF: 0.0362

Gnomad4 OTH exome AF: 0.0428

GnomAD4 genome AF: 0.0329 AC: 5001 AN: 152194 Hom.: 140 Cov.: 33 AF XY: 0.0349 AC XY: 2595 AN XY: 74384

Gnomad4 AFR AF: 0.00670

Gnomad4 AMR AF: 0.0190

Gnomad4 ASJ AF: 0.0565

Gnomad4 EAS AF: 0.0722

Gnomad4 SAS AF: 0.0834

Gnomad4 FIN AF: 0.0630

Gnomad4 NFE AF: 0.0396

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0343 Hom.: 69

Bravo AF: 0.0277

Asia WGS AF: 0.102 AC: 356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	11
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00041
dbscSNV1_RF	Benign	0.0080
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: rs2291175; hg19: chr13-99062978;