Genetic Variant FARP1:c.*4118T>C (chr13-98452435-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_005766.4(FARP1):c.*4118T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,488 control chromosomes in the GnomAD database, including 4,037 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 ( 4031 hom., cov: 32)

Exomes 𝑓: 0.18 ( 6 hom. )

Consequence

FARP1
NM_005766.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.247

Publications

10 publications found

Variant links:

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]

FARP1 links:

STK24 (HGNC:11403): (serine/threonine kinase 24) This gene encodes a serine/threonine protein kinase that functions upstream of mitogen-activated protein kinase (MAPK) signaling. The encoded protein is cleaved into two chains by caspases; the N-terminal fragment (MST3/N) translocates to the nucleus and promotes programmed cells death. There is a pseudogene for this gene on chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

STK24 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FARP1	NM_005766.4 link	c.*4118T>C		3_prime_UTR_variant	Exon 27 of 27	ENST00000319562.11	NP_005757.1
STK24	NM_001032296.4 link	c.*738A>G		3_prime_UTR_variant	Exon 11 of 11	ENST00000539966.6	NP_001027467.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FARP1	ENST00000319562.11 link	c.*4118T>C		3_prime_UTR_variant	Exon 27 of 27	1	NM_005766.4	ENSP00000322926.6
STK24	ENST00000539966.6 link	c.*738A>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_001032296.4	ENSP00000442539.2

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34296

AN:

151928

Hom.:

4017

Cov.:

show subpopulations

Gnomad AFR

AF:

0.264

Gnomad AMI

AF:

0.196

Gnomad AMR

AF:

0.187

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.158

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.168

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.224

Gnomad OTH

AF:

0.228

GnomAD4 exome

AF:

0.176

AC:

AN:

442

Hom.:

Cov.:

AF XY:

0.193

AC XY:

AN XY:

264

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.173

AC:

AN:

428

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.226

AC:

34338

AN:

152046

Hom.:

4031

Cov.:

AF XY:

0.222

AC XY:

16491

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.264

AC:

10942

AN:

41426

American (AMR)

AF:

0.187

AC:

2861

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.240

AC:

831

AN:

3468

East Asian (EAS)

AF:

0.159

AC:

821

AN:

5174

South Asian (SAS)

AF:

0.231

AC:

1113

AN:

4812

European-Finnish (FIN)

AF:

0.168

AC:

1775

AN:

10578

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.224

AC:

15244

AN:

67986

Other (OTH)

AF:

0.233

AC:

491

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1373

2745

4118

5490

6863

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

360

720

1080

1440

1800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.224

Hom.:

7503

Bravo

AF:

0.226

Asia WGS

AF:

0.212

AC:

736

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

0.25

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over