rs12490991

Variant names:

• chr3-16415588-A-G
• rs12490991
• NM_015150.2:c.333-6105T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-16415588-A-G
• chr3-16415588-A-T

Variant summary

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

The NM_015150.2(RFTN1):​c.333-6105T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 151,030 control chromosomes in the GnomAD database, including 6,930 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 0.29 (6930 hom., cov: 28)
• Consequence: RFTN1 NM_015150.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.488
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFTN1	NM_015150.2	c.333-6105T>C		intron_variant	Intron 3 of 9	ENST00000334133.9	NP_055965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFTN1	ENST00000334133.9	c.333-6105T>C		intron_variant	Intron 3 of 9	1	NM_015150.2	ENSP00000334153.4

Frequencies

GnomAD3 genomes AF: 0.290 AC: 43748 AN: 150914 Hom.: 6919 Cov.: 28

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.290 AC: 43784 AN: 151030 Hom.: 6930 Cov.: 28 AF XY: 0.288 AC XY: 21253 AN XY: 73730

African (AFR) AF: 0.155 AC: 6402 AN: 41320

American (AMR) AF: 0.343 AC: 5192 AN: 15118

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1304 AN: 3448

East Asian (EAS) AF: 0.310 AC: 1586 AN: 5114

South Asian (SAS) AF: 0.264 AC: 1255 AN: 4750

European-Finnish (FIN) AF: 0.342 AC: 3545 AN: 10360

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.349 AC: 23616 AN: 67626

Other (OTH) AF: 0.302 AC: 633 AN: 2098

Alfa AF: 0.287 Hom.: 3023

Bravo AF: 0.284

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.70
PhyloP100		-0.49
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: rs12490991; hg19: chr3-16457095;