4-37635094-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001085400.2(RELL1):​c.473C>T​(p.Pro158Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000396 in 1,614,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

RELL1
NM_001085400.2 missense

Scores

3
5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.06
Variant links:
Genes affected
RELL1 (HGNC:27379): (RELT like 1) Involved in positive regulation of p38MAPK cascade. Located in microtubule cytoskeleton and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16435882).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RELL1NM_001085400.2 linkc.473C>T p.Pro158Leu missense_variant 5/7 ENST00000454158.7 NP_001078869.1 Q8IUW5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RELL1ENST00000454158.7 linkc.473C>T p.Pro158Leu missense_variant 5/75 NM_001085400.2 ENSP00000398778.2 Q8IUW5
RELL1ENST00000314117.8 linkc.473C>T p.Pro158Leu missense_variant 5/71 ENSP00000313385.4 Q8IUW5
RELL1ENST00000512114.1 linkc.536C>T p.Pro179Leu missense_variant 5/53 ENSP00000424031.1 D6RBN9

Frequencies

GnomAD3 genomes
AF:
0.000151
AC:
23
AN:
152196
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000602
AC:
15
AN:
249328
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135276
show subpopulations
Gnomad AFR exome
AF:
0.000775
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000274
AC:
40
AN:
1461864
Hom.:
0
Cov.:
32
AF XY:
0.0000206
AC XY:
15
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.000597
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000989
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.000158
AC:
24
AN:
152314
Hom.:
0
Cov.:
33
AF XY:
0.000175
AC XY:
13
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.000505
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000115
Hom.:
0
Bravo
AF:
0.000162
ESP6500AA
AF:
0.00103
AC:
4
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000745
AC:
9

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 29, 2024The c.473C>T (p.P158L) alteration is located in exon 5 (coding exon 5) of the RELL1 gene. This alteration results from a C to T substitution at nucleotide position 473, causing the proline (P) at amino acid position 158 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.29
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
T;T;.
Eigen
Pathogenic
0.82
Eigen_PC
Pathogenic
0.82
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.85
.;D;D
M_CAP
Benign
0.034
D
MetaRNN
Benign
0.16
T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Uncertain
2.7
M;M;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-3.5
D;D;D
REVEL
Benign
0.20
Sift
Benign
0.11
T;T;T
Sift4G
Uncertain
0.0030
D;D;.
Polyphen
1.0
D;D;.
Vest4
0.63
MVP
0.20
MPC
1.3
ClinPred
0.48
T
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.21
gMVP
0.68

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: rs369636478; hg19: chr4-37636716; API