rs9990208

Positions:

• chr3-16504579-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015150.2(RFTN1):​c.-9+8863G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,166 control chromosomes in the GnomAD database, including 1,826 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 0.14 (1826 hom., cov: 32)
• Consequence: RFTN1 NM_015150.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.857

Genes affected

RFTN1 (HGNC:30278): (raftlin, lipid raft linker 1) Enables double-stranded RNA binding activity. Involved in B cell receptor signaling pathway; membrane raft assembly; and positive regulation of growth rate. Acts upstream of or within dsRNA transport; response to exogenous dsRNA; and toll-like receptor 3 signaling pathway. Located in endosome; membrane raft; and plasma membrane. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFTN1	NM_015150.2	c.-9+8863G>A		intron_variant		ENST00000334133.9	NP_055965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFTN1	ENST00000334133.9	c.-9+8863G>A		intron_variant		1	NM_015150.2	ENSP00000334153.4

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20859 AN: 152048 Hom.: 1819 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.0402

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0927

Gnomad OTH AF: 0.127

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.137 AC: 20889 AN: 152166 Hom.: 1826 Cov.: 32 AF XY: 0.136 AC XY: 10111 AN XY: 74384

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.0398

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.0927

Gnomad4 OTH AF: 0.124

Alfa AF: 0.0980 Hom.: 472

Bravo AF: 0.142

Asia WGS AF: 0.103 AC: 358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.60

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

Other links and lift over

dbSNP: rs9990208; hg19: chr3-16546086;