rs1570070

Variant names:

• chr6-160032946-A-G
• rs1570070
• NM_000876.4:c.1050A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000876.4(IGF2R):​c.1050A>G​(p.Ser350Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,577,878 control chromosomes in the GnomAD database, including 99,156 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S350S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.33 (8942 hom., cov: 32)
  • Exomes 𝑓: 0.35 (90214 hom.)
• Consequence: IGF2R NM_000876.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107
• Publications: 28 publications found

Genes affected

IGF2R (HGNC:5467): (insulin like growth factor 2 receptor) This gene encodes a receptor for both insulin-like growth factor 2 and mannose 6-phosphate. The binding sites for each ligand are located on different segments of the protein. This receptor has various functions, including in the intracellular trafficking of lysosomal enzymes, the activation of transforming growth factor beta, and the degradation of insulin-like growth factor 2. Mutation or loss of heterozygosity of this gene has been association with risk of hepatocellular carcinoma. The orthologous mouse gene is imprinted and shows exclusive expression from the maternal allele; however, imprinting of the human gene may be polymorphic, as only a minority of individuals showed biased expression from the maternal allele (PMID:8267611). [provided by RefSeq, Nov 2015]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-0.107 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000876.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2R	NM_000876.4	MANE Select	c.1050A>G	p.Ser350Ser	synonymous	Exon 9 of 48	NP_000867.3	P11717

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2R	ENST00000356956.6	TSL:1 MANE Select	c.1050A>G	p.Ser350Ser	synonymous	Exon 9 of 48	ENSP00000349437.1	P11717
	IGF2R	ENST00000649737.1		n.287A>G		non_coding_transcript_exon	Exon 2 of 3
	IGF2R	ENST00000676781.1		n.1050A>G		non_coding_transcript_exon	Exon 9 of 49	ENSP00000504419.1	A0A7I2YQS7

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50237 AN: 151972 Hom.: 8941 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.334

GnomAD2 exomes AF: 0.379 AC: 94554 AN: 249624 AF XY: 0.378

Gnomad AFR exome AF: 0.255

Gnomad AMR exome AF: 0.444

Gnomad ASJ exome AF: 0.250

Gnomad EAS exome AF: 0.744

Gnomad FIN exome AF: 0.323

Gnomad NFE exome AF: 0.333

Gnomad OTH exome AF: 0.352

GnomAD4 exome AF: 0.346 AC: 492965 AN: 1425788 Hom.: 90214 Cov.: 29 AF XY: 0.348 AC XY: 247170 AN XY: 711208

African (AFR) AF: 0.247 AC: 8071 AN: 32726

American (AMR) AF: 0.435 AC: 19296 AN: 44342

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 6475 AN: 25926

East Asian (EAS) AF: 0.741 AC: 29232 AN: 39452

South Asian (SAS) AF: 0.405 AC: 34468 AN: 85012

European-Finnish (FIN) AF: 0.321 AC: 17078 AN: 53256

Middle Eastern (MID) AF: 0.333 AC: 1890 AN: 5668

European-Non Finnish (NFE) AF: 0.329 AC: 355818 AN: 1080354

Other (OTH) AF: 0.349 AC: 20637 AN: 59052

GnomAD4 genome AF: 0.330 AC: 50249 AN: 152090 Hom.: 8942 Cov.: 32 AF XY: 0.334 AC XY: 24837 AN XY: 74344

African (AFR) AF: 0.257 AC: 10673 AN: 41484

American (AMR) AF: 0.378 AC: 5770 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 868 AN: 3470

East Asian (EAS) AF: 0.746 AC: 3859 AN: 5172

South Asian (SAS) AF: 0.426 AC: 2055 AN: 4822

European-Finnish (FIN) AF: 0.312 AC: 3288 AN: 10550

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22655 AN: 67996

Other (OTH) AF: 0.339 AC: 716 AN: 2110

Alfa AF: 0.334 Hom.: 16678

Bravo AF: 0.333

Asia WGS AF: 0.579 AC: 2015 AN: 3478

EpiCase AF: 0.329

EpiControl AF: 0.329

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.30
PhyloP100		-0.11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs1570070; hg19: chr6-160453978; COSMIC: COSV63627556;