Genetic Variant NM_024660.4:c.656C>T (chr19-35739775-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024660.4(IGFLR1):c.656C>T(p.Ser219Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,413,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 7.1e-7 ( 0 hom. )

Consequence

IGFLR1
NM_024660.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08722073).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFLR1	NM_024660.4 link	c.656C>T	p.Ser219Phe	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.656C>T	p.Ser219Phe	missense_variant	Exon 4 of 5	1	NM_024660.4	ENSP00000246532.1	Q9H665-1
ENSG00000267120	ENST00000589807.1 link	n.*1150C>T		non_coding_transcript_exon_variant	Exon 10 of 11	2		ENSP00000472696.1	M0R2N4
ENSG00000267120	ENST00000589807.1 link	n.*1150C>T		3_prime_UTR_variant	Exon 10 of 11	2		ENSP00000472696.1	M0R2N4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000460

AC:

AN:

217184

AF XY:

0.00

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:

0.0000101

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.07e-7

AC:

AN:

1413830

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

696708

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32456

American (AMR)

AF:

0.00

AC:

AN:

40910

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22668

East Asian (EAS)

AF:

0.00

AC:

AN:

39188

South Asian (SAS)

AF:

0.00

AC:

AN:

78502

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51438

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5536

European-Non Finnish (NFE)

AF:

9.22e-7

AC:

AN:

1084892

Other (OTH)

AF:

0.00

AC:

AN:

58240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 04, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.656C>T (p.S219F) alteration is located in exon 4 (coding exon 3) of the IGFLR1 gene. This alteration results from a C to T substitution at nucleotide position 656, causing the serine (S) at amino acid position 219 to be replaced by a phenylalanine (F). 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

0.11

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.066

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.56

.;T

M_CAP

Benign

0.047

MetaRNN

Benign

0.087

T;T

MetaSVM

Benign

-0.64

MutationAssessor

Benign

1.6

L;L

PhyloP100

1.3

PrimateAI

Benign

0.25

PROVEAN

Benign

-2.1

N;.

REVEL

Benign

0.082

Sift

Benign

0.078

T;.

Sift4G

Uncertain

0.055

T;T

Polyphen

0.020

B;B

Vest4

0.17

MutPred

0.23

Loss of glycosylation at S219 (P = 0.0031);Loss of glycosylation at S219 (P = 0.0031);

MVP

0.35

MPC

0.098

ClinPred

0.071

GERP RS

-0.018

Varity_R

0.097

gMVP

0.36

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over