rs2291174

chr13-98410859-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.1692+36A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0869 in 1,080,338 control chromosomes in the GnomAD database, including 4,614 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 0.073 (497 hom., cov: 33)
  • Exomes 𝑓: 0.089 (4117 hom.)
• Consequence: FARP1 NM_005766.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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 (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FARP1	NM_005766.4	c.1692+36A>G		intron_variant		ENST00000319562.11
FARP1	NM_001286839.2	c.1692+36A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FARP1	ENST00000319562.11	c.1692+36A>G		intron_variant		1	NM_005766.4	P1
FARP1	ENST00000595437.5	c.1692+36A>G		intron_variant		1
FARP1	ENST00000627049.2	c.1692+36A>G		intron_variant		5
FARP1	ENST00000457029.3	n.330+36A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0735 AC: 11185 AN: 152096 Hom.: 497 Cov.: 33

Gnomad AFR AF: 0.0237

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0655

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0723

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0941

Gnomad OTH AF: 0.0802

GnomAD3 exomes AF: 0.0866 AC: 16376 AN: 188998 Hom.: 783 AF XY: 0.0891 AC XY: 8966 AN XY: 100574

Gnomad AFR exome AF: 0.0218

Gnomad AMR exome AF: 0.0563

Gnomad ASJ exome AF: 0.101

Gnomad EAS exome AF: 0.117

Gnomad SAS exome AF: 0.0772

Gnomad FIN exome AF: 0.116

Gnomad NFE exome AF: 0.0959

Gnomad OTH exome AF: 0.0973

GnomAD4 exome AF: 0.0891 AC: 82710 AN: 928124 Hom.: 4117 Cov.: 12 AF XY: 0.0895 AC XY: 42630 AN XY: 476288

Gnomad4 AFR exome AF: 0.0229

Gnomad4 AMR exome AF: 0.0548

Gnomad4 ASJ exome AF: 0.0988

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.0741

Gnomad4 FIN exome AF: 0.115

Gnomad4 NFE exome AF: 0.0916

Gnomad4 OTH exome AF: 0.0875

GnomAD4 genome AF: 0.0735 AC: 11184 AN: 152214 Hom.: 497 Cov.: 33 AF XY: 0.0752 AC XY: 5596 AN XY: 74418

Gnomad4 AFR AF: 0.0237

Gnomad4 AMR AF: 0.0653

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.0727

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.0941

Gnomad4 OTH AF: 0.0794

Alfa AF: 0.0888 Hom.: 901

Bravo AF: 0.0685

Asia WGS AF: 0.0790 AC: 272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.038
Dann	Benign	0.49
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: rs2291174; hg19: chr13-99063113; COSMIC: COSV60336720; COSMIC: COSV60336720;