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GeneBe

3-16377845-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_015150.2(RFTN1):c.699C>T(p.Leu233=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00765 in 1,614,190 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0054 ( 5 hom., cov: 33)
Exomes 𝑓: 0.0079 ( 60 hom. )

Consequence

RFTN1
NM_015150.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.02
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-16377845-G-A is Benign according to our data. Variant chr3-16377845-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2653608.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.02 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RFTN1NM_015150.2 linkuse as main transcriptc.699C>T p.Leu233= synonymous_variant 5/10 ENST00000334133.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RFTN1ENST00000334133.9 linkuse as main transcriptc.699C>T p.Leu233= synonymous_variant 5/101 NM_015150.2 P1
RFTN1ENST00000432519.5 linkuse as main transcriptc.591C>T p.Leu197= synonymous_variant 4/91
RFTN1ENST00000451036.5 linkuse as main transcriptc.699C>T p.Leu233= synonymous_variant 5/54
RFTN1ENST00000495666.5 linkuse as main transcript downstream_gene_variant 4

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00545
AC:
829
AN:
152194
Hom.:
5
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00157
Gnomad AMI
AF:
0.00329
Gnomad AMR
AF:
0.00321
Gnomad ASJ
AF:
0.00835
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00786
Gnomad FIN
AF:
0.00273
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00894
Gnomad OTH
AF:
0.00382
GnomAD3 exomes
AF:
0.00625
AC:
1571
AN:
251388
Hom.:
8
AF XY:
0.00656
AC XY:
891
AN XY:
135876
show subpopulations
Gnomad AFR exome
AF:
0.00111
Gnomad AMR exome
AF:
0.00252
Gnomad ASJ exome
AF:
0.0112
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00712
Gnomad FIN exome
AF:
0.00397
Gnomad NFE exome
AF:
0.00888
Gnomad OTH exome
AF:
0.00619
GnomAD4 exome
AF:
0.00789
AC:
11527
AN:
1461878
Hom.:
60
Cov.:
32
AF XY:
0.00800
AC XY:
5819
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00116
Gnomad4 AMR exome
AF:
0.00224
Gnomad4 ASJ exome
AF:
0.0103
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.00735
Gnomad4 FIN exome
AF:
0.00489
Gnomad4 NFE exome
AF:
0.00874
Gnomad4 OTH exome
AF:
0.00715
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00544
AC:
829
AN:
152312
Hom.:
5
Cov.:
33
AF XY:
0.00513
AC XY:
382
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.00156
Gnomad4 AMR
AF:
0.00320
Gnomad4 ASJ
AF:
0.00835
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00807
Gnomad4 FIN
AF:
0.00273
Gnomad4 NFE
AF:
0.00892
Gnomad4 OTH
AF:
0.00378
Alfa
AF:
0.00821
Hom.:
4
Bravo
AF:
0.00552
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.00851
EpiControl
AF:
0.00812

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenDec 01, 2022RFTN1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
Cadd
Benign
0.30
Dann
Benign
0.44

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs61739728; hg19: chr3-16419352; COSMIC: COSV61917111; COSMIC: COSV61917111; API