3-16386974-C-T

Variant names:

• chr3-16386974-C-T
• rs12629276
• NM_015150.2:c.442-8872G>A

Variant summary

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

The NM_015150.2(RFTN1):​c.442-8872G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,166 control chromosomes in the GnomAD database, including 3,067 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 0.18 (3067 hom., cov: 32)
• Consequence: RFTN1 NM_015150.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.873
• Publications: 6 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=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFTN1	NM_015150.2	c.442-8872G>A		intron_variant	Intron 4 of 9	ENST00000334133.9	NP_055965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFTN1	ENST00000334133.9	c.442-8872G>A		intron_variant	Intron 4 of 9	1	NM_015150.2	ENSP00000334153.4

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27569 AN: 152048 Hom.: 3061 Cov.: 32

Gnomad AFR AF: 0.0783

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.181 AC: 27592 AN: 152166 Hom.: 3067 Cov.: 32 AF XY: 0.188 AC XY: 14006 AN XY: 74384

African (AFR) AF: 0.0782 AC: 3248 AN: 41540

American (AMR) AF: 0.227 AC: 3469 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 528 AN: 3472

East Asian (EAS) AF: 0.449 AC: 2326 AN: 5178

South Asian (SAS) AF: 0.365 AC: 1758 AN: 4822

European-Finnish (FIN) AF: 0.231 AC: 2446 AN: 10568

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13269 AN: 67986

Other (OTH) AF: 0.193 AC: 407 AN: 2110

Alfa AF: 0.192 Hom.: 1561

Bravo AF: 0.170

Asia WGS AF: 0.374 AC: 1300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.1
DANN	Benign	0.37
PhyloP100		-0.87
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: rs12629276; hg19: chr3-16428481;