17-31517693-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032932.6(RAB11FIP4):​c.379A>T​(p.Ile127Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 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. 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. I127V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RAB11FIP4 NM_032932.6 missense
• Clinical Significance: Not reported in ClinVar
• 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: 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=0.050041467).

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>T	p.Ile127Phe	missense	Exon 4 of 15	NP_116321.2
	RAB11FIP4	NM_001303542.3		c.73A>T	p.Ile25Phe	missense	Exon 2 of 13	NP_001290471.2	Q86YS3-2
	RAB11FIP4	NM_001346747.2		c.73A>T	p.Ile25Phe	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>T	p.Ile127Phe	missense	Exon 4 of 15	ENSP00000482620.1	Q86YS3-1
	RAB11FIP4	ENST00000964368.1		c.379A>T	p.Ile127Phe	missense	Exon 4 of 15	ENSP00000634427.1
	RAB11FIP4	ENST00000394744.6	TSL:2	c.73A>T	p.Ile25Phe	missense	Exon 2 of 13	ENSP00000378227.2	Q86YS3-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455296 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 722988

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

American (AMR) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109484

Other (OTH) AF: 0.00 AC: 0 AN: 60210

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.86
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.60
PrimateAI	Benign	0.40	T
REVEL	Benign	0.026
Sift4G	Benign	0.29	T
Polyphen		0.028	B
Vest4		0.18
MutPred		0.13		Gain of loop (P = 0.0166)
MVP		0.043
ClinPred		0.069	T
GERP RS		-0.72
Varity_R		0.038
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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;