rs12487874

Variant names:

• chr3-16465158-C-A
• rs12487874
• NM_015150.2:c.145+28567G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_015150.2(RFTN1):​c.145+28567G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 151,236 control chromosomes in the GnomAD database, including 2,540 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 0.16 (2540 hom., cov: 31)
• Consequence: RFTN1 NM_015150.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.948
• Publications: 1 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFTN1	NM_015150.2	c.145+28567G>T		intron_variant	Intron 2 of 9	ENST00000334133.9	NP_055965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFTN1	ENST00000334133.9	c.145+28567G>T		intron_variant	Intron 2 of 9	1	NM_015150.2	ENSP00000334153.4

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24788 AN: 151120 Hom.: 2540 Cov.: 31

Gnomad AFR AF: 0.0449

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.164 AC: 24794 AN: 151236 Hom.: 2540 Cov.: 31 AF XY: 0.161 AC XY: 11908 AN XY: 73814

African (AFR) AF: 0.0448 AC: 1843 AN: 41182

American (AMR) AF: 0.183 AC: 2781 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 827 AN: 3458

East Asian (EAS) AF: 0.101 AC: 519 AN: 5154

South Asian (SAS) AF: 0.160 AC: 768 AN: 4788

European-Finnish (FIN) AF: 0.158 AC: 1627 AN: 10300

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15786 AN: 67846

Other (OTH) AF: 0.203 AC: 425 AN: 2094

Alfa AF: 0.205 Hom.: 6191

Bravo AF: 0.162

Asia WGS AF: 0.114 AC: 399 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Benign	0.83
PhyloP100		0.95
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: rs12487874; hg19: chr3-16506665;