chr6-159984057-A-G

Variant names:

• chr6-159984057-A-G
• rs3798197
• NM_000876.4:c.150-7127A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000876.4(IGF2R):​c.150-7127A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,062 control chromosomes in the GnomAD database, including 10,284 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 0.36 (10284 hom., cov: 32)
• Consequence: IGF2R NM_000876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 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.150-7127A>G		intron	N/A	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.150-7127A>G		intron	N/A	ENSP00000349437.1	P11717
	IGF2R	ENST00000676781.1		n.150-7127A>G		intron	N/A	ENSP00000504419.1	A0A7I2YQS7
	IGF2R	ENST00000677704.1		n.150-7127A>G		intron	N/A	ENSP00000503314.1	A0A7I2V381

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53904 AN: 151944 Hom.: 10238 Cov.: 32

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.330

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.355 AC: 54005 AN: 152062 Hom.: 10284 Cov.: 32 AF XY: 0.367 AC XY: 27288 AN XY: 74322

African (AFR) AF: 0.410 AC: 17010 AN: 41468

American (AMR) AF: 0.353 AC: 5395 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 990 AN: 3470

East Asian (EAS) AF: 0.708 AC: 3654 AN: 5164

South Asian (SAS) AF: 0.453 AC: 2183 AN: 4820

European-Finnish (FIN) AF: 0.424 AC: 4476 AN: 10560

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.283 AC: 19250 AN: 67982

Other (OTH) AF: 0.338 AC: 715 AN: 2116

Alfa AF: 0.305 Hom.: 6945

Bravo AF: 0.351

Asia WGS AF: 0.569 AC: 1982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.050
DANN	Benign	0.60
PhyloP100		-1.2
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: rs3798197; hg19: chr6-160405089;