rs12635698

Positions:

• chr3-16366982-T-C

Variant summary

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

The NM_015150.2(RFTN1):​c.1030+3094A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 151,486 control chromosomes in the GnomAD database, including 4,643 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 0.22 (4643 hom., cov: 33)
• Consequence: RFTN1 NM_015150.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.328

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFTN1	NM_015150.2	c.1030+3094A>G		intron_variant		ENST00000334133.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFTN1	ENST00000334133.9	c.1030+3094A>G		intron_variant		1	NM_015150.2	P1
RFTN1	ENST00000432519.5	c.922+3094A>G		intron_variant		1
	ENST00000653928.1	n.348-2697T>C		intron_variant, non_coding_transcript_variant
RFTN1	ENST00000483671.1	n.309+3094A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32846 AN: 151366 Hom.: 4632 Cov.: 33

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.0308

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0593

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.217 AC: 32901 AN: 151486 Hom.: 4643 Cov.: 33 AF XY: 0.197 AC XY: 14515 AN XY: 73762

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.0307

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.0593

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.222

Alfa AF: 0.148 Hom.: 4648

Asia WGS AF: 0.124 AC: 433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.3
DANN	Benign	0.66

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: rs12635698; hg19: chr3-16408489;