3-16460937-T-C

Variant names:

• chr3-16460937-T-C
• rs1517521
• NM_015150.2:c.146-26900A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015150.2(RFTN1):​c.146-26900A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,134 control chromosomes in the GnomAD database, including 3,168 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 0.19 (3168 hom., cov: 32)
• Consequence: RFTN1 NM_015150.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFTN1	NM_015150.2	c.146-26900A>G		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.146-26900A>G		intron_variant	Intron 2 of 9	1	NM_015150.2	ENSP00000334153.4

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28800 AN: 152016 Hom.: 3149 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.190 AC: 28868 AN: 152134 Hom.: 3168 Cov.: 32 AF XY: 0.189 AC XY: 14025 AN XY: 74378

African (AFR) AF: 0.288 AC: 11953 AN: 41484

American (AMR) AF: 0.137 AC: 2092 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 634 AN: 3470

East Asian (EAS) AF: 0.258 AC: 1331 AN: 5160

South Asian (SAS) AF: 0.122 AC: 590 AN: 4826

European-Finnish (FIN) AF: 0.187 AC: 1983 AN: 10598

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

European-Non Finnish (NFE) AF: 0.143 AC: 9711 AN: 67982

Other (OTH) AF: 0.181 AC: 383 AN: 2116

Alfa AF: 0.158 Hom.: 776

Bravo AF: 0.192

Asia WGS AF: 0.222 AC: 774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.1
DANN	Benign	0.35
PhyloP100		-0.32
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: rs1517521; hg19: chr3-16502444;