rs2291175

Variant names:

• chr13-98410724-G-T
• rs2291175
• NM_005766.4:c.1603-10G>T

Variant summary

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

The NM_005766.4(FARP1):​c.1603-10G>T variant causes a 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 intron
• Scores: Splicing: ADA: 0.0004121
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313
• Publications: 4 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=-0.72).
• 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 rank	MANE	Protein	UniProt
FARP1	NM_005766.4	c.1603-10G>T		intron_variant	Intron 14 of 26	ENST00000319562.11	NP_005757.1
FARP1	NM_001286839.2	c.1603-10G>T		intron_variant	Intron 14 of 27		NP_001273768.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FARP1	ENST00000319562.11	c.1603-10G>T		intron_variant	Intron 14 of 26	1	NM_005766.4	ENSP00000322926.6
FARP1	ENST00000595437.5	c.1603-10G>T		intron_variant	Intron 14 of 27	1		ENSP00000471242.1
FARP1	ENST00000627049.2	c.1603-10G>T		intron_variant	Intron 14 of 27	5		ENSP00000486285.1
FARP1	ENST00000457029.3	n.241-10G>T		intron_variant	Intron 2 of 5	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

GnomAD2 exomes AF: 0.0466 AC: 10832 AN: 232450 AF XY: 0.0497

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 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

African (AFR) AF: 0.00617 AC: 196 AN: 31764

American (AMR) AF: 0.0168 AC: 719 AN: 42764

Ashkenazi Jewish (ASJ) AF: 0.0558 AC: 1381 AN: 24762

East Asian (EAS) AF: 0.0580 AC: 2256 AN: 38902

South Asian (SAS) AF: 0.0838 AC: 6827 AN: 81464

European-Finnish (FIN) AF: 0.0603 AC: 3150 AN: 52282

Middle Eastern (MID) AF: 0.0409 AC: 228 AN: 5572

European-Non Finnish (NFE) AF: 0.0362 AC: 37238 AN: 1028880

Other (OTH) AF: 0.0428 AC: 2435 AN: 56948

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

African (AFR) AF: 0.00670 AC: 278 AN: 41516

American (AMR) AF: 0.0190 AC: 291 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 196 AN: 3468

East Asian (EAS) AF: 0.0722 AC: 374 AN: 5182

South Asian (SAS) AF: 0.0834 AC: 402 AN: 4820

European-Finnish (FIN) AF: 0.0630 AC: 667 AN: 10580

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0396 AC: 2692 AN: 68012

Other (OTH) AF: 0.0440 AC: 93 AN: 2114

Alfa AF: 0.0341 Hom.: 76

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
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2291175; hg19: chr13-99062978;