Genetic Variant RAB11FIP4:p.Cys84Arg (chr17-31434036-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_032932.6(RAB11FIP4):c.250T>C(p.Cys84Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000063 in 1,428,240 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

RAB11FIP4
NM_032932.6 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.96

Publications

0 publications found

Variant links:

Genes affected

RAB11FIP4 (HGNC:30267): (RAB11 family interacting protein 4) The protein encoded by this gene interacts with RAB11 and is thought to be involved in bringing recycling endosome membranes to the cleavage furrow in late cytokinesis. Hypoxic conditions can lead to an upregulation of the encoded protein and enhance the metastatic potential of hepatocellular carcinoma. [provided by RefSeq, Oct 2016]

RAB11FIP4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 9 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032932.6. 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
	RAB11FIP4	NM_032932.6	MANE Select	c.250T>C	p.Cys84Arg	missense splice_region	Exon 3 of 15	NP_116321.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAB11FIP4	ENST00000621161.5	TSL:1 MANE Select	c.250T>C	p.Cys84Arg	missense splice_region	Exon 3 of 15	ENSP00000482620.1	Q86YS3-1
RAB11FIP4	ENST00000964368.1		c.250T>C	p.Cys84Arg	missense splice_region	Exon 3 of 15	ENSP00000634427.1
RAB11FIP4	ENST00000582009.5	TSL:3	c.118T>C	p.Cys40Arg	missense splice_region	Exon 3 of 5	ENSP00000463206.1	J3QKR9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000977

AC:

AN:

204722

AF XY:

0.00000908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000127

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000630

AC:

AN:

1428240

Hom.:

Cov.:

AF XY:

0.00000423

AC XY:

AN XY:

708394

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33374

American (AMR)

AF:

0.00

AC:

AN:

39796

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25524

East Asian (EAS)

AF:

0.000103

AC:

AN:

38962

South Asian (SAS)

AF:

0.00

AC:

AN:

82086

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5622

European-Non Finnish (NFE)

AF:

0.00000453

AC:

AN:

1103856

Other (OTH)

AF:

0.00

AC:

AN:

59712

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.26

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.81

M_CAP

Benign

0.037

MetaRNN

Uncertain

0.49

MetaSVM

Benign

-0.64

MutationAssessor

Benign

1.6

PhyloP100

4.0

PrimateAI

Uncertain

0.61

Sift4G

Benign

0.10

Polyphen

1.0

Vest4

0.84

MutPred

0.49

Gain of disorder (P = 0.0359)

MVP

0.33

ClinPred

0.77

GERP RS

4.8

Varity_R

0.48

gMVP

0.80

Mutation Taster

=66/34

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