dbSNP rs377051797: RAB11FIP1:p.Arg439Leu (chr8-37870391-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000524118.1(RAB11FIP1):c.1316G>T(p.Arg439Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000169 in 1,182,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R439H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000017 ( 0 hom. )

Consequence

RAB11FIP1
ENST00000524118.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.584

Publications

2 publications found

Variant links:

Genes affected

RAB11FIP1 (HGNC:30265): (RAB11 family interacting protein 1) This gene encodes one of the Rab11-family interacting proteins (Rab11-FIPs), which play a role in the Rab-11 mediated recycling of vesicles. The encoded protein may be involved in endocytic sorting, trafficking of proteins including integrin subunits and epidermal growth factor receptor (EGFR), and transport between the recycling endosome and the trans-Golgi network. Alternative splicing results in multiple transcript variants. A pseudogene is described on the X chromosome. [provided by RefSeq, Dec 2013]

RAB11FIP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07286197).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000524118.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB11FIP1	NM_001002814.3	MANE Select	c.3633+29G>T		intron	N/A	NP_001002814.2	Q6WKZ4-4
	RAB11FIP1	NM_025151.5		c.1731+29G>T		intron	N/A	NP_079427.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAB11FIP1	ENST00000524118.1	TSL:1	c.1316G>T	p.Arg439Leu	missense	Exon 3 of 3	ENSP00000430680.1	Q6WKZ4-2
RAB11FIP1	ENST00000330843.9	TSL:1 MANE Select	c.3633+29G>T		intron	N/A	ENSP00000331342.4	Q6WKZ4-4
RAB11FIP1	ENST00000287263.8	TSL:1	c.1731+29G>T		intron	N/A	ENSP00000287263.4	Q6WKZ4-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

246032

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000169

AC:

AN:

1182604

Hom.:

Cov.:

AF XY:

0.00000167

AC XY:

AN XY:

600278

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27874

American (AMR)

AF:

0.00

AC:

AN:

43820

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24350

East Asian (EAS)

AF:

0.00

AC:

AN:

38004

South Asian (SAS)

AF:

0.00

AC:

AN:

79698

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53150

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5238

European-Non Finnish (NFE)

AF:

0.00000233

AC:

AN:

859274

Other (OTH)

AF:

0.00

AC:

AN:

51196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.68

(source)

DANN

Benign

0.90

Eigen

Benign

-0.86

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.33

M_CAP

Benign

0.0027

MetaRNN

Benign

0.073

MetaSVM

Benign

-1.1

PhyloP100

-0.58

PROVEAN

Benign

1.8

REVEL

Benign

0.036

Sift

Pathogenic

0.0

Polyphen

0.0080

Vest4

0.18

MutPred

0.38

Gain of stability (P = 0.0053)

MVP

0.45

ClinPred

0.067

GERP RS

-0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=99/1

polymorphism

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over