Genetic Variant RAB11FIP4:p.Ser8Pro (chr17-31391874-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032932.6(RAB11FIP4):c.22T>C(p.Ser8Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000017 in 1,175,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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. S8A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 30)

Exomes 𝑓: 9.7e-7 ( 0 hom. )

Consequence

RAB11FIP4
NM_032932.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0690

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:

ENSG00000306303 (HGNC:):

ENSG00000306303 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034384906).

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.22T>C	p.Ser8Pro	missense	Exon 1 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.22T>C	p.Ser8Pro	missense	Exon 1 of 15	ENSP00000482620.1	Q86YS3-1
RAB11FIP4	ENST00000964368.1		c.22T>C	p.Ser8Pro	missense	Exon 1 of 15	ENSP00000634427.1
ENSG00000306303	ENST00000816883.1		n.170+388A>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000677

AC:

AN:

147630

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.73e-7

AC:

AN:

1027724

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

488510

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20538

American (AMR)

AF:

0.00

AC:

AN:

6226

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11358

East Asian (EAS)

AF:

0.00

AC:

AN:

20536

South Asian (SAS)

AF:

0.00

AC:

AN:

20506

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17932

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2594

European-Non Finnish (NFE)

AF:

0.00000112

AC:

AN:

888920

Other (OTH)

AF:

0.00

AC:

AN:

39114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000677

AC:

AN:

147630

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71880

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40790

American (AMR)

AF:

0.00

AC:

AN:

14890

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3404

East Asian (EAS)

AF:

0.00

AC:

AN:

5064

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9228

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000151

AC:

AN:

66194

Other (OTH)

AF:

0.00

AC:

AN:

2040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.52

DEOGEN2

Benign

0.015

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.092

LIST_S2

Benign

0.21

M_CAP

Benign

0.079

MetaRNN

Benign

0.034

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.81

PhyloP100

-0.069

PrimateAI

Pathogenic

0.92

Sift4G

Benign

0.35

Polyphen

0.0

Vest4

0.12

MutPred

0.20

Gain of relative solvent accessibility (P = 0.0249)

MVP

0.043

ClinPred

0.039

GERP RS

1.7

PromoterAI

0.034

Neutral

(source)

Varity_R

0.079

gMVP

0.28

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over