chr8-37870391-C-T

Variant names:

• chr8-37870391-C-T
• rs377051797
• ENST00000524118.1:c.1316G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000524118.1(RAB11FIP1):​c.1316G>A​(p.Arg439His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00394 in 1,334,836 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (15 hom.)
• Consequence: RAB11FIP1 ENST00000524118.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.584
• Publications: 2 publications found

Genes affected

RAB11FIP1 (HGNC:30265): (RAB11 family interacting protein 1) This gene encodes one of the Rab11-family interacting proteins (Rab11-FIPs), which play a role in the Rab-11 mediated recycling of vesicles. The encoded protein may be involved in endocytic sorting, trafficking of proteins including integrin subunits and epidermal growth factor receptor (EGFR), and transport between the recycling endosome and the trans-Golgi network. Alternative splicing results in multiple transcript variants. A pseudogene is described on the X chromosome. [provided by RefSeq, Dec 2013]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004038751).
• BP6: Variant 8-37870391-C-T is Benign according to our data. Variant chr8-37870391-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2658539.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 15 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000524118.1. 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
	RAB11FIP1	NM_001002814.3	MANE Select	c.3633+29G>A		intron	N/A	NP_001002814.2	Q6WKZ4-4
	RAB11FIP1	NM_025151.5		c.1731+29G>A		intron	N/A	NP_079427.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB11FIP1	ENST00000524118.1	TSL:1	c.1316G>A	p.Arg439His	missense	Exon 3 of 3	ENSP00000430680.1	Q6WKZ4-2
	RAB11FIP1	ENST00000330843.9	TSL:1 MANE Select	c.3633+29G>A		intron	N/A	ENSP00000331342.4	Q6WKZ4-4
	RAB11FIP1	ENST00000287263.8	TSL:1	c.1731+29G>A		intron	N/A	ENSP00000287263.4	Q6WKZ4-3

Frequencies

GnomAD3 genomes AF: 0.00311 AC: 473 AN: 152172 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00520

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00275 AC: 677 AN: 246032 AF XY: 0.00266

Gnomad AFR exome AF: 0.000880

Gnomad AMR exome AF: 0.00158

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00126

Gnomad NFE exome AF: 0.00506

Gnomad OTH exome AF: 0.00235

GnomAD4 exome AF: 0.00405 AC: 4788 AN: 1182546 Hom.: 15 Cov.: 16 AF XY: 0.00390 AC XY: 2340 AN XY: 600252

African (AFR) AF: 0.000718 AC: 20 AN: 27874

American (AMR) AF: 0.00203 AC: 89 AN: 43820

Ashkenazi Jewish (ASJ) AF: 0.0000821 AC: 2 AN: 24350

East Asian (EAS) AF: 0.0000263 AC: 1 AN: 38004

South Asian (SAS) AF: 0.000151 AC: 12 AN: 79698

European-Finnish (FIN) AF: 0.00149 AC: 79 AN: 53150

Middle Eastern (MID) AF: 0.000382 AC: 2 AN: 5238

European-Non Finnish (NFE) AF: 0.00509 AC: 4370 AN: 859222

Other (OTH) AF: 0.00416 AC: 213 AN: 51190

GnomAD4 genome AF: 0.00311 AC: 473 AN: 152290 Hom.: 1 Cov.: 32 AF XY: 0.00299 AC XY: 223 AN XY: 74464

African (AFR) AF: 0.00101 AC: 42 AN: 41558

American (AMR) AF: 0.00392 AC: 60 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00520 AC: 354 AN: 68034

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00284 Hom.: 1

Bravo AF: 0.00327

TwinsUK AF: 0.00485 AC: 18

ALSPAC AF: 0.00597 AC: 23

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00547 AC: 47

ExAC AF: 0.00295 AC: 358

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.6
DANN	Uncertain	0.98
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.58
PROVEAN	Benign	0.63	N
REVEL	Benign	0.016
Sift	Pathogenic	0.0	D
Polyphen		0.0030	B
Vest4		0.045
MVP		0.34
ClinPred		0.0090	T
GERP RS		-0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	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: rs377051797; hg19: chr8-37727909;