NM_014808.4:c.-25+646A>G

Variant names:

• chr2-241357034-A-G
• rs1476698
• NM_014808.4:c.-25+646A>G

Variant summary

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

The NM_014808.4(FARP2):​c.-25+646A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,134 control chromosomes in the GnomAD database, including 12,236 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 0.39 (12236 hom., cov: 33)
• Consequence: FARP2 NM_014808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990
• Publications: 40 publications found

Genes affected

FARP2 (HGNC:16460): (FERM, ARH/RhoGEF and pleckstrin domain protein 2) Enables guanyl-nucleotide exchange factor activity. Acts upstream of or within Rac protein signal transduction and neuron remodeling. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014808.4. 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
	FARP2	NM_014808.4	MANE Select	c.-25+646A>G		intron	N/A	NP_055623.1
	FARP2	NM_001282983.2		c.-25+646A>G		intron	N/A	NP_001269912.1
	FARP2	NM_001282984.2		c.-25+646A>G		intron	N/A	NP_001269913.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FARP2	ENST00000264042.8	TSL:1 MANE Select	c.-25+646A>G		intron	N/A	ENSP00000264042.3
	FARP2	ENST00000373287.8	TSL:1	c.-25+646A>G		intron	N/A	ENSP00000362384.4
	FARP2	ENST00000627550.2	TSL:2	c.-25+646A>G		intron	N/A	ENSP00000486597.1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59735 AN: 152016 Hom.: 12199 Cov.: 33

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.399

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.393 AC: 59829 AN: 152134 Hom.: 12236 Cov.: 33 AF XY: 0.397 AC XY: 29557 AN XY: 74368

African (AFR) AF: 0.383 AC: 15871 AN: 41472

American (AMR) AF: 0.504 AC: 7699 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1026 AN: 3472

East Asian (EAS) AF: 0.671 AC: 3466 AN: 5166

South Asian (SAS) AF: 0.439 AC: 2118 AN: 4828

European-Finnish (FIN) AF: 0.408 AC: 4315 AN: 10584

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24239 AN: 68012

Other (OTH) AF: 0.404 AC: 852 AN: 2110

Alfa AF: 0.373 Hom.: 26071

Bravo AF: 0.401

Asia WGS AF: 0.580 AC: 2018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.4
DANN	Benign	0.42
PhyloP100		0.099
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: rs1476698; hg19: chr2-242296449;