chr13-98390136-T-C

Variant names:

• chr13-98390136-T-C
• rs2256823
• NM_005766.4:c.1019+16T>C

Variant summary

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

The NM_001286839.2(FARP1):​c.1019+16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,609,740 control chromosomes in the GnomAD database, including 38,571 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 0.29 (8392 hom., cov: 32)
  • Exomes 𝑓: 0.19 (30179 hom.)
• Consequence: FARP1 NM_001286839.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.544 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.1019+16T>C		intron	N/A	NP_005757.1
	FARP1	NM_001286839.2		c.1019+16T>C		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.1019+16T>C		intron	N/A	ENSP00000322926.6
	FARP1	ENST00000595437.5	TSL:1	c.1019+16T>C		intron	N/A	ENSP00000471242.1
	FARP1	ENST00000871505.1		c.1019+16T>C		intron	N/A	ENSP00000541564.1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43736 AN: 151996 Hom.: 8365 Cov.: 32

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.259

GnomAD2 exomes AF: 0.224 AC: 55629 AN: 248758 AF XY: 0.216

Gnomad AFR exome AF: 0.558

Gnomad AMR exome AF: 0.265

Gnomad ASJ exome AF: 0.179

Gnomad EAS exome AF: 0.238

Gnomad FIN exome AF: 0.166

Gnomad NFE exome AF: 0.174

Gnomad OTH exome AF: 0.201

GnomAD4 exome AF: 0.192 AC: 279720 AN: 1457626 Hom.: 30179 Cov.: 32 AF XY: 0.192 AC XY: 139022 AN XY: 724750

African (AFR) AF: 0.562 AC: 18718 AN: 33278

American (AMR) AF: 0.259 AC: 11455 AN: 44216

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 4816 AN: 25930

East Asian (EAS) AF: 0.282 AC: 11175 AN: 39658

South Asian (SAS) AF: 0.230 AC: 19741 AN: 85738

European-Finnish (FIN) AF: 0.171 AC: 9128 AN: 53268

Middle Eastern (MID) AF: 0.204 AC: 1165 AN: 5710

European-Non Finnish (NFE) AF: 0.172 AC: 191271 AN: 1109608

Other (OTH) AF: 0.203 AC: 12251 AN: 60220

GnomAD4 genome AF: 0.288 AC: 43814 AN: 152114 Hom.: 8392 Cov.: 32 AF XY: 0.287 AC XY: 21375 AN XY: 74376

African (AFR) AF: 0.550 AC: 22808 AN: 41476

American (AMR) AF: 0.232 AC: 3551 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 637 AN: 3470

East Asian (EAS) AF: 0.246 AC: 1267 AN: 5158

South Asian (SAS) AF: 0.242 AC: 1169 AN: 4826

European-Finnish (FIN) AF: 0.178 AC: 1881 AN: 10586

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.173 AC: 11779 AN: 67998

Other (OTH) AF: 0.257 AC: 544 AN: 2114

Alfa AF: 0.254 Hom.: 1442

Bravo AF: 0.305

Asia WGS AF: 0.276 AC: 961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.2
DANN	Benign	0.30
PhyloP100		0.053
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2256823; hg19: chr13-99042390; COSMIC: COSV60330358; COSMIC: COSV60330358;