Genetic Variant RAB11FIP1:p.Arg439His (chr8-37870391-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000524118.1(RAB11FIP1):c.1316G>A(p.Arg439His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00394 in 1,334,836 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0031 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 15 hom. )

Consequence

RAB11FIP1
ENST00000524118.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.584

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004038751).

BP6

Variant 8-37870391-C-T is Benign according to our data. Variant chr8-37870391-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2658539.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB11FIP1	NM_001002814.3 link	c.3633+29G>A		intron_variant	Intron 5 of 5	ENST00000330843.9	NP_001002814.2	Q6WKZ4-4
RAB11FIP1	NM_025151.5 link	c.1731+29G>A		intron_variant	Intron 4 of 4		NP_079427.4	Q6WKZ4-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB11FIP1	ENST00000330843.9 link	c.3633+29G>A		intron_variant	Intron 5 of 5	1	NM_001002814.3	ENSP00000331342.4		Q6WKZ4-4

Frequencies

GnomAD3 genomes

AF:

0.00311

AC:

473

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00520

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00275

AC:

677

AN:

246032

Hom.:

AF XY:

0.00266

AC XY:

354

AN XY:

132878

show subpopulations

Gnomad AFR exome

AF:

0.000880

Gnomad AMR exome

AF:

0.00158

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000101

Gnomad FIN exome

AF:

0.00126

Gnomad NFE exome

AF:

0.00506

Gnomad OTH exome

AF:

0.00235

GnomAD4 exome

AF:

0.00405

AC:

4788

AN:

1182546

Hom.:

Cov.:

AF XY:

0.00390

AC XY:

2340

AN XY:

600252

show subpopulations

Gnomad4 AFR exome

AF:

0.000718

Gnomad4 AMR exome

AF:

0.00203

Gnomad4 ASJ exome

AF:

0.0000821

Gnomad4 EAS exome

AF:

0.0000263

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00149

Gnomad4 NFE exome

AF:

0.00509

Gnomad4 OTH exome

AF:

0.00416

GnomAD4 genome

AF:

0.00311

AC:

473

AN:

152290

Hom.:

Cov.:

AF XY:

0.00299

AC XY:

223

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00520

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00350

Hom.:

Bravo

AF:

0.00327

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00547

AC:

ExAC

AF:

0.00295

AC:

358

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RAB11FIP1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.68

CADD

Benign

1.6

DANN

Uncertain

0.98

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.38

M_CAP

Benign

0.0024

MetaRNN

Benign

0.0040

MetaSVM

Benign

-1.0

PROVEAN

Benign

0.63

REVEL

Benign

0.016

Sift

Pathogenic

0.0

Polyphen

0.0030

Vest4

0.045

MVP

0.34

ClinPred

0.0090

GERP RS

-0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over