Variant chr2-73088140-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001371272.1(RAB11FIP5):c.1478C>T(p.Ala493Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000516 in 1,614,080 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00034 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00053 ( 12 hom. )

Consequence

RAB11FIP5
NM_001371272.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.96

Variant links:

Genes affected

RAB11FIP5 (HGNC:24845): (RAB11 family interacting protein 5) Enables gamma-tubulin binding activity. Involved in cellular response to acidic pH; negative regulation of adiponectin secretion; and regulation of protein localization to cell surface. Located in centriolar satellite and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

RAB11FIP5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048882365).

BP6

Variant 2-73088140-G-A is Benign according to our data. Variant chr2-73088140-G-A is described in ClinVar as [Benign]. Clinvar id is 771332.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000534 (781/1461812) while in subpopulation AMR AF= 0.0171 (767/44724). AF 95% confidence interval is 0.0161. There are 12 homozygotes in gnomad4_exome. There are 311 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB11FIP5	NM_001371272.1 linkuse as main transcript	c.1478C>T	p.Ala493Val	missense_variant	3/6	ENST00000486777.7
RAB11FIP5	NM_015470.3 linkuse as main transcript	c.1478C>T	p.Ala493Val	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
RAB11FIP5	ENST00000486777.7 linkuse as main transcript	c.1478C>T	p.Ala493Val	missense_variant	3/6	5	NM_001371272.1
RAB11FIP5	ENST00000258098.6 linkuse as main transcript	c.1478C>T	p.Ala493Val	missense_variant	3/5	1		P1
RAB11FIP5	ENST00000479196.1 linkuse as main transcript	n.189C>T		non_coding_transcript_exon_variant	1/2	3
RAB11FIP5	ENST00000493523.2 linkuse as main transcript	n.1387C>T		non_coding_transcript_exon_variant	2/4	2

Frequencies

GnomAD3 genomes

AF:

0.000342

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00273

AC:

687

AN:

251344

Hom.:

AF XY:

0.00205

AC XY:

279

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.0198

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000534

AC:

781

AN:

1461812

Hom.:

Cov.:

AF XY:

0.000428

AC XY:

311

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0171

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000342

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000428

Hom.:

Bravo

AF:

0.00119

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00235

AC:

285

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

T;T

Eigen

Benign

0.068

Eigen_PC

Benign

0.020

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.70

T;T

MetaRNN

Benign

0.0049

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.6

.;L

MutationTaster

Benign

0.55

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.45

.;N

REVEL

Benign

0.085

Sift

Benign

0.13

.;T

Sift4G

Benign

0.52

.;T

Polyphen

0.99

.;D

Vest4

0.15

MVP

0.61

MPC

0.22

ClinPred

0.030

GERP RS

2.6

Varity_R

0.023

gMVP

0.26

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