13-98385833-C-T

Variant names:

• chr13-98385833-C-T
• rs584800
• NM_005766.4:c.759+19C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286839.2(FARP1):​c.759+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,611,108 control chromosomes in the GnomAD database, including 31,271 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 0.23 (4424 hom., cov: 32)
  • Exomes 𝑓: 0.19 (26847 hom.)
• Consequence: FARP1 NM_001286839.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.399
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286839.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FARP1	NM_005766.4	MANE Select	c.759+19C>T		intron	N/A	NP_005757.1
	FARP1	NM_001286839.2		c.759+19C>T		intron	N/A	NP_001273768.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FARP1	ENST00000319562.11	TSL:1 MANE Select	c.759+19C>T		intron	N/A	ENSP00000322926.6
	FARP1	ENST00000595437.5	TSL:1	c.759+19C>T		intron	N/A	ENSP00000471242.1
	FARP1	ENST00000871505.1		c.759+19C>T		intron	N/A	ENSP00000541564.1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34878 AN: 152024 Hom.: 4409 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.221

GnomAD2 exomes AF: 0.205 AC: 51178 AN: 249376 AF XY: 0.201

Gnomad AFR exome AF: 0.347

Gnomad AMR exome AF: 0.250

Gnomad ASJ exome AF: 0.173

Gnomad EAS exome AF: 0.215

Gnomad FIN exome AF: 0.163

Gnomad NFE exome AF: 0.176

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.187 AC: 273522 AN: 1458966 Hom.: 26847 Cov.: 31 AF XY: 0.188 AC XY: 136242 AN XY: 725610

African (AFR) AF: 0.355 AC: 11872 AN: 33440

American (AMR) AF: 0.243 AC: 10884 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 4732 AN: 26124

East Asian (EAS) AF: 0.256 AC: 10154 AN: 39678

South Asian (SAS) AF: 0.223 AC: 19234 AN: 86192

European-Finnish (FIN) AF: 0.169 AC: 8868 AN: 52488

Middle Eastern (MID) AF: 0.204 AC: 1168 AN: 5734

European-Non Finnish (NFE) AF: 0.176 AC: 195164 AN: 1110304

Other (OTH) AF: 0.190 AC: 11446 AN: 60306

GnomAD4 genome AF: 0.230 AC: 34930 AN: 152142 Hom.: 4424 Cov.: 32 AF XY: 0.231 AC XY: 17152 AN XY: 74376

African (AFR) AF: 0.344 AC: 14276 AN: 41472

American (AMR) AF: 0.210 AC: 3213 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 627 AN: 3472

East Asian (EAS) AF: 0.222 AC: 1152 AN: 5180

South Asian (SAS) AF: 0.233 AC: 1126 AN: 4824

European-Finnish (FIN) AF: 0.176 AC: 1859 AN: 10572

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12076 AN: 68004

Other (OTH) AF: 0.218 AC: 460 AN: 2110

Alfa AF: 0.207 Hom.: 829

Bravo AF: 0.239

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.8
DANN	Benign	0.45
PhyloP100		0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs584800; hg19: chr13-99038087; COSMIC: COSV60349074; COSMIC: COSV60349074;