NM_000618.5:c.5G>C

Variant names:

• chr12-102480377-C-G
• rs3730195
• NM_000618.5:c.5G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000618.5(IGF1):​c.5G>C​(p.Gly2Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,152 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: IGF1 NM_000618.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.04

Genes affected

IGF1 (HGNC:5464): (insulin like growth factor 1) The protein encoded by this gene is similar to insulin in function and structure and is a member of a family of proteins involved in mediating growth and development. The encoded protein is processed from a precursor, bound by a specific receptor, and secreted. Defects in this gene are a cause of insulin-like growth factor I deficiency. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar processing to generate mature protein. [provided by RefSeq, Sep 2015]

LINC02456 (HGNC:53389): (long intergenic non-protein coding RNA 2456)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1	NM_000618.5	c.5G>C	p.Gly2Ala	missense_variant	Exon 1 of 4	ENST00000337514.11	NP_000609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1	ENST00000337514.11	c.5G>C	p.Gly2Ala	missense_variant	Exon 1 of 4	1	NM_000618.5	ENSP00000337612.7

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152152 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74338

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000463 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	.;.;.;.;T
Eigen	Benign	0.071
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.92	.;.;D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.47	T;T;T;T;T
MetaSVM	Uncertain	-0.015	T
MutationAssessor	Benign	1.9	L;L;L;L;L
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.57	N;N;.;.;N
REVEL	Uncertain	0.31
Sift	Benign	0.047	D;D;.;.;D
Sift4G	Benign	0.11	T;T;.;.;T
Polyphen		0.19	.;.;.;.;B
Vest4		0.23
MutPred		0.24		Gain of catalytic residue at G2 (P = 0.0643);Gain of catalytic residue at G2 (P = 0.0643);Gain of catalytic residue at G2 (P = 0.0643);Gain of catalytic residue at G2 (P = 0.0643);Gain of catalytic residue at G2 (P = 0.0643);
MVP		1.0
MPC		1.2
ClinPred		0.70	D
GERP RS		5.2
Varity_R		0.086
gMVP		0.59

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

Other links and lift over

dbSNP: rs3730195; hg19: chr12-102874155;