rs894817

Variant names:

• chr6-160043257-G-A
• rs894817
• NM_000876.4:c.1590G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-160043257-G-A
• chr6-160043257-G-T

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.1590G>A​(p.Gly530Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,613,798 control chromosomes in the GnomAD database, including 95,465 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.

• Frequency:
  • Genomes: 𝑓 0.32 (8485 hom., cov: 33)
  • Exomes 𝑓: 0.34 (86980 hom.)
• Consequence: IGF2R NM_000876.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.628
• Publications: 24 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=-0.55).
• BP7: Synonymous conserved (PhyloP=0.628 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.727 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.1590G>A	p.Gly530Gly	synonymous	Exon 12 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.1590G>A	p.Gly530Gly	synonymous	Exon 12 of 48	ENSP00000349437.1	P11717
	IGF2R	ENST00000676781.1		n.1590G>A		non_coding_transcript_exon	Exon 12 of 49	ENSP00000504419.1	A0A7I2YQS7
	IGF2R	ENST00000677704.1		n.1590G>A		non_coding_transcript_exon	Exon 12 of 49	ENSP00000503314.1	A0A7I2V381

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48887 AN: 152052 Hom.: 8478 Cov.: 33

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.326

GnomAD2 exomes AF: 0.362 AC: 90935 AN: 251384 AF XY: 0.359

Gnomad AFR exome AF: 0.273

Gnomad AMR exome AF: 0.437

Gnomad ASJ exome AF: 0.238

Gnomad EAS exome AF: 0.743

Gnomad FIN exome AF: 0.268

Gnomad NFE exome AF: 0.314

Gnomad OTH exome AF: 0.336

GnomAD4 exome AF: 0.335 AC: 489673 AN: 1461628 Hom.: 86980 Cov.: 36 AF XY: 0.336 AC XY: 244100 AN XY: 727112

African (AFR) AF: 0.269 AC: 9002 AN: 33476

American (AMR) AF: 0.428 AC: 19121 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 6278 AN: 26134

East Asian (EAS) AF: 0.740 AC: 29371 AN: 39694

South Asian (SAS) AF: 0.386 AC: 33313 AN: 86246

European-Finnish (FIN) AF: 0.269 AC: 14344 AN: 53408

Middle Eastern (MID) AF: 0.327 AC: 1888 AN: 5768

European-Non Finnish (NFE) AF: 0.320 AC: 355850 AN: 1111822

Other (OTH) AF: 0.340 AC: 20506 AN: 60380

GnomAD4 genome AF: 0.321 AC: 48904 AN: 152170 Hom.: 8485 Cov.: 33 AF XY: 0.323 AC XY: 24050 AN XY: 74394

African (AFR) AF: 0.274 AC: 11374 AN: 41510

American (AMR) AF: 0.370 AC: 5659 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 830 AN: 3472

East Asian (EAS) AF: 0.747 AC: 3866 AN: 5178

South Asian (SAS) AF: 0.407 AC: 1965 AN: 4824

European-Finnish (FIN) AF: 0.254 AC: 2686 AN: 10580

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21465 AN: 68002

Other (OTH) AF: 0.332 AC: 700 AN: 2108

Alfa AF: 0.319 Hom.: 16778

Bravo AF: 0.328

Asia WGS AF: 0.573 AC: 1994 AN: 3478

EpiCase AF: 0.312

EpiControl AF: 0.312

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	6.8
DANN	Benign	0.65
PhyloP100		0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs894817; hg19: chr6-160464289; COSMIC: COSV63627581;