chr8-37870435-A-G

Variant names:

• chr8-37870435-A-G
• rs140616452
• NM_001002814.3:c.3618T>C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001002814.3(RAB11FIP1):​c.3618T>C​(p.Asn1206Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00456 in 1,603,104 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (42 hom.)
• Consequence: RAB11FIP1 NM_001002814.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.30
• Publications: 0 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 8-37870435-A-G is Benign according to our data. Variant chr8-37870435-A-G is described in ClinVar as Benign. ClinVar VariationId is 791274.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.3 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.00455 (6599/1450798) while in subpopulation AMR AF = 0.0174 (778/44690). AF 95% confidence interval is 0.0164. There are 42 homozygotes in GnomAdExome4. There are 3190 alleles in the male GnomAdExome4 subpopulation. Median coverage is 28. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002814.3. 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.3618T>C	p.Asn1206Asn	synonymous	Exon 5 of 6	NP_001002814.2	Q6WKZ4-4
	RAB11FIP1	NM_025151.5		c.1716T>C	p.Asn572Asn	synonymous	Exon 4 of 5	NP_079427.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB11FIP1	ENST00000330843.9	TSL:1 MANE Select	c.3618T>C	p.Asn1206Asn	synonymous	Exon 5 of 6	ENSP00000331342.4	Q6WKZ4-4
	RAB11FIP1	ENST00000287263.8	TSL:1	c.1716T>C	p.Asn572Asn	synonymous	Exon 4 of 5	ENSP00000287263.4	Q6WKZ4-3
	RAB11FIP1	ENST00000522727.5	TSL:1	c.1272T>C	p.Asn424Asn	synonymous	Exon 4 of 5	ENSP00000430009.1	E7EX40

Frequencies

GnomAD3 genomes AF: 0.00473 AC: 720 AN: 152188 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000989

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.00884

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0186

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00491

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00652 AC: 1637 AN: 251168 AF XY: 0.00564

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.0192

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0208

Gnomad NFE exome AF: 0.00414

Gnomad OTH exome AF: 0.00555

GnomAD4 exome AF: 0.00455 AC: 6599 AN: 1450798 Hom.: 42 Cov.: 28 AF XY: 0.00441 AC XY: 3190 AN XY: 722558

African (AFR) AF: 0.000842 AC: 28 AN: 33240

American (AMR) AF: 0.0174 AC: 778 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26074

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.000407 AC: 35 AN: 85980

European-Finnish (FIN) AF: 0.0214 AC: 1143 AN: 53416

Middle Eastern (MID) AF: 0.000527 AC: 3 AN: 5688

European-Non Finnish (NFE) AF: 0.00401 AC: 4421 AN: 1102034

Other (OTH) AF: 0.00317 AC: 190 AN: 60030

GnomAD4 genome AF: 0.00472 AC: 719 AN: 152306 Hom.: 4 Cov.: 32 AF XY: 0.00521 AC XY: 388 AN XY: 74474

African (AFR) AF: 0.000986 AC: 41 AN: 41564

American (AMR) AF: 0.00876 AC: 134 AN: 15296

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0186 AC: 198 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00491 AC: 334 AN: 68036

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.00384 Hom.: 0

Bravo AF: 0.00412

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: 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
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.20
DANN	Benign	0.67
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs140616452; hg19: chr8-37727953;