dbSNP rs759167271: IGFLR1:p.Gly205Arg (chr19-35739818-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_024660.4(IGFLR1):c.613G>A(p.Gly205Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000552 in 1,449,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

IGFLR1
NM_024660.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.958

Publications

1 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]

IGFLR1 links:

ENSG00000267120 (HGNC:):

ENSG00000267120 links:

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=0.04881972).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFLR1	NM_024660.4 link	c.613G>A	p.Gly205Arg	missense_variant	Exon 4 of 5	ENST00000246532.6	NP_078936.1	Q9H665-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IGFLR1	ENST00000246532.6 link	c.613G>A	p.Gly205Arg	missense_variant	Exon 4 of 5	1	NM_024660.4	ENSP00000246532.1	Q9H665-1
ENSG00000267120	ENST00000589807.1 link	n.*1107G>A		non_coding_transcript_exon_variant	Exon 10 of 11	2		ENSP00000472696.1	M0R2N4
ENSG00000267120	ENST00000589807.1 link	n.*1107G>A		3_prime_UTR_variant	Exon 10 of 11	2		ENSP00000472696.1	M0R2N4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000163

AC:

AN:

244874

AF XY:

0.0000303

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000362

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000552

AC:

AN:

1449426

Hom.:

Cov.:

AF XY:

0.00000834

AC XY:

AN XY:

719054

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33308

American (AMR)

AF:

0.00

AC:

AN:

44280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25372

East Asian (EAS)

AF:

0.00

AC:

AN:

39468

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84900

European-Finnish (FIN)

AF:

0.0000189

AC:

AN:

52958

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.00000544

AC:

AN:

1103588

Other (OTH)

AF:

0.00

AC:

AN:

59846

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000287

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 28, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.613G>A (p.G205R) 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 613, causing the glycine (G) at amino acid position 205 to be replaced by an arginine (R). 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

0.087

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.46

CADD

Benign

0.45

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.051

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.38

.;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.049

T;T

MetaSVM

Benign

-0.43

MutationAssessor

Benign

1.0

L;L

PhyloP100

-0.96

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.050

N;.

REVEL

Benign

0.10

Sift

Benign

0.29

T;.

Sift4G

Uncertain

0.039

D;D

Polyphen

0.015

B;B

Vest4

0.11

MutPred

0.32

Gain of catalytic residue at G205 (P = 0.0308);Gain of catalytic residue at G205 (P = 0.0308);

MVP

0.22

MPC

0.10

ClinPred

0.065

GERP RS

-8.3

Varity_R

0.12

gMVP

0.17

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs759167271

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over