rs576547327

Variant names:

• chr19-35739300-A-G
• rs576547327
• NM_024660.4:c.1048T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024660.4(IGFLR1):​c.1048T>C​(p.Ser350Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000338 in 1,597,042 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: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: IGFLR1 NM_024660.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.807
• Publications: 5 publications found

Genes affected

IGFLR1 (HGNC:23620): (IGF like family receptor 1) Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267120 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0066196322).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFLR1	NM_024660.4	c.1048T>C	p.Ser350Pro	missense_variant	Exon 5 of 5	ENST00000246532.6	NP_078936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFLR1	ENST00000246532.6	c.1048T>C	p.Ser350Pro	missense_variant	Exon 5 of 5	1	NM_024660.4	ENSP00000246532.1
ENSG00000267120	ENST00000589807.1	n.*1542T>C		non_coding_transcript_exon_variant	Exon 11 of 11	2		ENSP00000472696.1
ENSG00000267120	ENST00000589807.1	n.*1542T>C		3_prime_UTR_variant	Exon 11 of 11	2		ENSP00000472696.1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152242 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000976 AC: 23 AN: 235686 AF XY: 0.000109

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00129

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000298 AC: 43 AN: 1444682 Hom.: 0 Cov.: 32 AF XY: 0.0000279 AC XY: 20 AN XY: 716064

African (AFR) AF: 0.00 AC: 0 AN: 33154

American (AMR) AF: 0.00 AC: 0 AN: 43598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25534

East Asian (EAS) AF: 0.00102 AC: 40 AN: 39182

South Asian (SAS) AF: 0.00 AC: 0 AN: 84908

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52046

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100968

Other (OTH) AF: 0.0000503 AC: 3 AN: 59604

GnomAD4 genome AF: 0.0000722 AC: 11 AN: 152360 Hom.: 0 Cov.: 33 AF XY: 0.0000805 AC XY: 6 AN XY: 74506

African (AFR) AF: 0.0000240 AC: 1 AN: 41584

American (AMR) AF: 0.00 AC: 0 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000341 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000990 AC: 12

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1048T>C (p.S350P) alteration is located in exon 5 (coding exon 4) of the IGFLR1 gene. This alteration results from a T to C substitution at nucleotide position 1048, causing the serine (S) at amino acid position 350 to be replaced by a proline (P). 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	0.094
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	3.5
DANN	Benign	0.81
DEOGEN2	Benign	0.0020	T;.;.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.32	.;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.0066	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;.;.;L
PhyloP100		-0.81
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.15	N;.;.;.
REVEL	Benign	0.028
Sift	Benign	0.24	T;.;.;.
Sift4G	Benign	0.15	T;T;T;T
Polyphen		0.0020	B;B;.;B
Vest4		0.13
MutPred		0.25		Loss of MoRF binding (P = 0.0173);.;.;Loss of MoRF binding (P = 0.0173);
MVP		0.11
MPC		0.22
ClinPred		0.019	T
GERP RS		-3.4
Varity_R		0.079
gMVP		0.32
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs576547327; hg19: chr19-36230201;