Genetic Variant NM_001371272.1:c.2125_2136dupGGAGGAGGAGGA (chr2-73081095-T-TTCCTCCTCCTCC) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001371272.1(RAB11FIP5):c.2125_2136dupGGAGGAGGAGGA(p.Gly709_Gly712dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RAB11FIP5
NM_001371272.1 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0420

Publications

1 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001371272.1

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB11FIP5	NM_001371272.1 link	c.2125_2136dupGGAGGAGGAGGA	p.Gly709_Gly712dup	conservative_inframe_insertion	Exon 4 of 6	ENST00000486777.7	NP_001358201.1
RAB11FIP5	NM_015470.3 link	c.1569-4925_1569-4914dupGGAGGAGGAGGA		intron_variant	Intron 3 of 4		NP_056285.1	Q9BXF6Q9UFM0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB11FIP5	ENST00000486777.7 link	c.2125_2136dupGGAGGAGGAGGA	p.Gly709_Gly712dup	conservative_inframe_insertion	Exon 4 of 6	5	NM_001371272.1	ENSP00000489752.1		A0A1B0GTL5

Frequencies

GnomAD3 genomes

AF:

0.00000668

AC:

AN:

149636

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000246

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000115

AC:

124

AN:

1080158

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

510572

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000439

AC:

AN:

22776

American (AMR)

AF:

0.00

AC:

AN:

8438

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14386

East Asian (EAS)

AF:

0.00

AC:

AN:

26490

South Asian (SAS)

AF:

0.00

AC:

AN:

19508

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21534

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2954

European-Non Finnish (NFE)

AF:

0.000133

AC:

122

AN:

920342

Other (OTH)

AF:

0.0000229

AC:

AN:

43730

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.381

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000668

AC:

AN:

149636

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72980

show subpopulations

African (AFR)

AF:

0.0000246

AC:

AN:

40700

American (AMR)

AF:

0.00

AC:

AN:

15084

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3442

East Asian (EAS)

AF:

0.00

AC:

AN:

4988

South Asian (SAS)

AF:

0.00

AC:

AN:

4726

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10344

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67094

Other (OTH)

AF:

0.00

AC:

AN:

2046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

103

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.042

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_001371272.1:c.2125_2136dupGGAGGAGGAGGA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over