13-98440840-C-T

Variant names:

• chr13-98440840-C-T
• rs2146998
• NM_005766.4:c.2796+4C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005766.4(FARP1):​c.2796+4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000264 in 1,596,118 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: FARP1 NM_005766.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.883

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FARP1	NM_005766.4	c.2796+4C>T		splice_region_variant, intron_variant	Intron 24 of 26	ENST00000319562.11	NP_005757.1
FARP1	NM_001286839.2	c.2889+4C>T		splice_region_variant, intron_variant	Intron 25 of 27		NP_001273768.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FARP1	ENST00000319562.11	c.2796+4C>T		splice_region_variant, intron_variant	Intron 24 of 26	1	NM_005766.4	ENSP00000322926.6
FARP1	ENST00000595437.5	c.2889+4C>T		splice_region_variant, intron_variant	Intron 25 of 27	1		ENSP00000471242.1
FARP1	ENST00000627049.2	c.2889+4C>T		splice_region_variant, intron_variant	Intron 25 of 27	5		ENSP00000486285.1
FARP1	ENST00000596256.1	c.*44C>T		downstream_gene_variant		3		ENSP00000469365.1

Frequencies

GnomAD3 genomes AF: 0.00139 AC: 211 AN: 152214 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00470

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.000148 AC: 213 AN: 1443786 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 97 AN XY: 717254

Gnomad4 AFR exome AF: 0.00375

Gnomad4 AMR exome AF: 0.000570

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000425

Gnomad4 OTH exome AF: 0.000284

GnomAD4 genome AF: 0.00137 AC: 208 AN: 152332 Hom.: 0 Cov.: 33 AF XY: 0.00137 AC XY: 102 AN XY: 74492

Gnomad4 AFR AF: 0.00462

Gnomad4 AMR AF: 0.000784

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000462 Hom.: 0

Bravo AF: 0.00160

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2146998; hg19: chr13-99093094;