rs2291174

Variant names:

• chr13-98410859-A-G
• rs2291174
• NM_005766.4:c.1692+36A>G

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.82).
• 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 rank	MANE	Protein	UniProt
FARP1	NM_005766.4	c.1692+36A>G		intron_variant	Intron 15 of 26	ENST00000319562.11	NP_005757.1
FARP1	NM_001286839.2	c.1692+36A>G		intron_variant	Intron 15 of 27		NP_001273768.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FARP1	ENST00000319562.11	c.1692+36A>G		intron_variant	Intron 15 of 26	1	NM_005766.4	ENSP00000322926.6
FARP1	ENST00000595437.5	c.1692+36A>G		intron_variant	Intron 15 of 27	1		ENSP00000471242.1
FARP1	ENST00000627049.2	c.1692+36A>G		intron_variant	Intron 15 of 27	5		ENSP00000486285.1
FARP1	ENST00000457029.3	n.330+36A>G		intron_variant	Intron 3 of 5	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

GnomAD2 exomes AF: 0.0866 AC: 16376 AN: 188998 AF XY: 0.0891

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 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

African (AFR) AF: 0.0229 AC: 540 AN: 23588

American (AMR) AF: 0.0548 AC: 2073 AN: 37808

Ashkenazi Jewish (ASJ) AF: 0.0988 AC: 2184 AN: 22098

East Asian (EAS) AF: 0.112 AC: 4037 AN: 36098

South Asian (SAS) AF: 0.0741 AC: 5237 AN: 70648

European-Finnish (FIN) AF: 0.115 AC: 5798 AN: 50250

Middle Eastern (MID) AF: 0.102 AC: 479 AN: 4712

European-Non Finnish (NFE) AF: 0.0916 AC: 58664 AN: 640664

Other (OTH) AF: 0.0875 AC: 3698 AN: 42258

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

African (AFR) AF: 0.0237 AC: 984 AN: 41552

American (AMR) AF: 0.0653 AC: 998 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 359 AN: 3468

East Asian (EAS) AF: 0.113 AC: 584 AN: 5166

South Asian (SAS) AF: 0.0727 AC: 351 AN: 4826

European-Finnish (FIN) AF: 0.116 AC: 1228 AN: 10584

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0941 AC: 6400 AN: 68022

Other (OTH) AF: 0.0794 AC: 168 AN: 2116

Alfa AF: 0.0863 Hom.: 1058

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
PhyloP100		-1.6
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: rs2291174; hg19: chr13-99063113; COSMIC: COSV60336720; COSMIC: COSV60336720;