17-31517693-A-G

Variant names:

• chr17-31517693-A-G
• rs748677479
• NM_032932.6:c.379A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_032932.6(RAB11FIP4):​c.379A>G​(p.Ile127Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000261 in 1,455,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: RAB11FIP4 NM_032932.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.599
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03839773).
• BS2: High AC in GnomAdExome4 at 38 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.379A>G	p.Ile127Val	missense	Exon 4 of 15	NP_116321.2
	RAB11FIP4	NM_001303542.3		c.73A>G	p.Ile25Val	missense	Exon 2 of 13	NP_001290471.2	Q86YS3-2
	RAB11FIP4	NM_001346747.2		c.73A>G	p.Ile25Val	missense	Exon 2 of 12	NP_001333676.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB11FIP4	ENST00000621161.5	TSL:1 MANE Select	c.379A>G	p.Ile127Val	missense	Exon 4 of 15	ENSP00000482620.1	Q86YS3-1
	RAB11FIP4	ENST00000964368.1		c.379A>G	p.Ile127Val	missense	Exon 4 of 15	ENSP00000634427.1
	RAB11FIP4	ENST00000394744.6	TSL:2	c.73A>G	p.Ile25Val	missense	Exon 2 of 13	ENSP00000378227.2	Q86YS3-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000169 AC: 4 AN: 236964 AF XY: 0.00000781

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000900

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: 0.000172

GnomAD4 exome AF: 0.0000261 AC: 38 AN: 1455296 Hom.: 0 Cov.: 34 AF XY: 0.0000290 AC XY: 21 AN XY: 722988

African (AFR) AF: 0.00 AC: 0 AN: 33430

American (AMR) AF: 0.0000912 AC: 4 AN: 43854

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25896

East Asian (EAS) AF: 0.00 AC: 0 AN: 39606

South Asian (SAS) AF: 0.00 AC: 0 AN: 84072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52984

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5760

European-Non Finnish (NFE) AF: 0.0000288 AC: 32 AN: 1109484

Other (OTH) AF: 0.0000166 AC: 1 AN: 60210

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Benign	0.84
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.60
PrimateAI	Benign	0.36	T
REVEL	Benign	0.031
Sift4G	Benign	1.0	T
Polyphen		0.0050	B
Vest4		0.084
MutPred		0.13		Gain of loop (P = 0.0166)
MVP		0.043
ClinPred		0.022	T
GERP RS		-0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.023
gMVP		0.11
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs748677479; hg19: chr17-29844711;