rs2038227

Variant names:

• chr16-489140-C-A
• rs2038227
• NM_014700.4:c.1265+140C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014700.4(RAB11FIP3):​c.1265+140C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 1,046,724 control chromosomes in the GnomAD database, including 186,856 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (29023 hom., cov: 33)
  • Exomes 𝑓: 0.59 (157833 hom.)
• Consequence: RAB11FIP3 NM_014700.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180
• Publications: 18 publications found

Genes affected

RAB11FIP3 (HGNC:17224): (RAB11 family interacting protein 3) Proteins of the large Rab GTPase family (see RAB1A; MIM 179508) have regulatory roles in the formation, targeting, and fusion of intracellular transport vesicles. RAB11FIP3 is one of many proteins that interact with and regulate Rab GTPases (Hales et al., 2001 [PubMed 11495908]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB11FIP3	NM_014700.4	c.1265+140C>A		intron_variant	Intron 5 of 13	ENST00000262305.9	NP_055515.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB11FIP3	ENST00000262305.9	c.1265+140C>A		intron_variant	Intron 5 of 13	1	NM_014700.4	ENSP00000262305.4

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93241 AN: 151900 Hom.: 29008 Cov.: 33

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.614

GnomAD4 exome AF: 0.590 AC: 527511 AN: 894706 Hom.: 157833 Cov.: 11 AF XY: 0.584 AC XY: 259244 AN XY: 443936

African (AFR) AF: 0.719 AC: 14109 AN: 19612

American (AMR) AF: 0.466 AC: 7484 AN: 16056

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 9197 AN: 15540

East Asian (EAS) AF: 0.490 AC: 14698 AN: 30024

South Asian (SAS) AF: 0.412 AC: 20332 AN: 49298

European-Finnish (FIN) AF: 0.616 AC: 18953 AN: 30780

Middle Eastern (MID) AF: 0.661 AC: 2188 AN: 3312

European-Non Finnish (NFE) AF: 0.604 AC: 417196 AN: 690616

Other (OTH) AF: 0.592 AC: 23354 AN: 39468

GnomAD4 genome AF: 0.614 AC: 93302 AN: 152018 Hom.: 29023 Cov.: 33 AF XY: 0.607 AC XY: 45067 AN XY: 74306

African (AFR) AF: 0.706 AC: 29283 AN: 41452

American (AMR) AF: 0.514 AC: 7854 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2115 AN: 3470

East Asian (EAS) AF: 0.472 AC: 2437 AN: 5166

South Asian (SAS) AF: 0.424 AC: 2045 AN: 4820

European-Finnish (FIN) AF: 0.607 AC: 6407 AN: 10560

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41108 AN: 67958

Other (OTH) AF: 0.612 AC: 1293 AN: 2112

Alfa AF: 0.601 Hom.: 47880

Bravo AF: 0.615

Asia WGS AF: 0.529 AC: 1843 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.61
DANN	Benign	0.51
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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: rs2038227; hg19: chr16-539140; COSMIC: COSV51932036; COSMIC: COSV51932036;