19-35739712-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024660.4(IGFLR1):​c.719G>A​(p.Arg240Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,401,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

IGFLR1
NM_024660.4 missense, splice_region

Scores

19
Splicing: ADA: 0.0001838
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.71

Publications

0 publications found
Variant links:
Genes affected
IGFLR1 (HGNC:23620): (IGF like family receptor 1) Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.034234315).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IGFLR1NM_024660.4 linkc.719G>A p.Arg240Lys missense_variant, splice_region_variant Exon 4 of 5 ENST00000246532.6 NP_078936.1 Q9H665-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IGFLR1ENST00000246532.6 linkc.719G>A p.Arg240Lys missense_variant, splice_region_variant Exon 4 of 5 1 NM_024660.4 ENSP00000246532.1 Q9H665-1
ENSG00000267120ENST00000589807.1 linkn.*1213G>A splice_region_variant, non_coding_transcript_exon_variant Exon 10 of 11 2 ENSP00000472696.1 M0R2N4
ENSG00000267120ENST00000589807.1 linkn.*1213G>A 3_prime_UTR_variant Exon 10 of 11 2 ENSP00000472696.1 M0R2N4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000143
AC:
2
AN:
1401502
Hom.:
0
Cov.:
32
AF XY:
0.00000145
AC XY:
1
AN XY:
689326
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31956
American (AMR)
AF:
0.00
AC:
0
AN:
38778
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
21804
East Asian (EAS)
AF:
0.0000256
AC:
1
AN:
39066
South Asian (SAS)
AF:
0.00
AC:
0
AN:
76678
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
50826
Middle Eastern (MID)
AF:
0.000183
AC:
1
AN:
5462
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1079232
Other (OTH)
AF:
0.00
AC:
0
AN:
57700
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 17, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.719G>A (p.R240K) alteration is located in exon 4 (coding exon 3) of the IGFLR1 gene. This alteration results from a G to A substitution at nucleotide position 719, causing the arginine (R) at amino acid position 240 to be replaced by a lysine (K). 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
0.089
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
0.32
DANN
Benign
0.76
DEOGEN2
Benign
0.0076
T;.;T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.080
N
LIST_S2
Benign
0.36
.;T;T
M_CAP
Benign
0.0044
T
MetaRNN
Benign
0.034
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.92
L;.;L
PhyloP100
-1.7
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.080
N;.;.
REVEL
Benign
0.010
Sift
Benign
1.0
T;.;.
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0010
B;.;B
Vest4
0.11
MutPred
0.27
Gain of ubiquitination at R240 (P = 0.006);.;Gain of ubiquitination at R240 (P = 0.006);
MVP
0.055
MPC
0.088
ClinPred
0.039
T
GERP RS
-6.9
Varity_R
0.076
gMVP
0.27
Mutation Taster
=91/9
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00018
dbscSNV1_RF
Benign
0.024
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

Other links and lift over

hg19: chr19-36230613; API