rs1004446

Positions:

• chr11-2148913-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000643349.2(ENSG00000284779):​c.254+213C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 594,250 control chromosomes in the GnomAD database, including 37,969 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 (10303 hom., cov: 31)
  • Exomes 𝑓: 0.35 (27666 hom.)
• Consequence: ENST00000643349.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214

Genes affected

(HGNC:):

IGF2 (HGNC:5466): (insulin like growth factor 2) This gene encodes a member of the insulin family of polypeptide growth factors, which are involved in development and growth. It is an imprinted gene, expressed only from the paternal allele, and epigenetic changes at this locus are associated with Wilms tumour, Beckwith-Wiedemann syndrome, rhabdomyosarcoma, and Silver-Russell syndrome. A read-through INS-IGF2 gene exists, whose 5' region overlaps the INS gene and the 3' region overlaps this gene. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INS-IGF2	NR_003512.4	n.466+213C>T		intron_variant, non_coding_transcript_variant
IGF2	NM_001007139.6	c.-249+213C>T		intron_variant			NP_001007140.2
INS-IGF2	NM_001042376.3	c.407+213C>T		intron_variant			NP_001035835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000643349.2	c.254+213C>T		intron_variant				ENSP00000495715	P1
IGF2	ENST00000481781.3	c.-249+213C>T		intron_variant		5		ENSP00000511998	P4
IGF2	ENST00000695541.1	c.-249+213C>T		intron_variant				ENSP00000511997	P4
IGF2	ENST00000476874.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55337 AN: 151632 Hom.: 10301 Cov.: 31

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.336

GnomAD4 exome AF: 0.348 AC: 154063 AN: 442500 Hom.: 27666 Cov.: 4 AF XY: 0.343 AC XY: 79583 AN XY: 231954

Gnomad4 AFR exome AF: 0.408

Gnomad4 AMR exome AF: 0.275

Gnomad4 ASJ exome AF: 0.338

Gnomad4 EAS exome AF: 0.304

Gnomad4 SAS exome AF: 0.273

Gnomad4 FIN exome AF: 0.345

Gnomad4 NFE exome AF: 0.369

Gnomad4 OTH exome AF: 0.354

GnomAD4 genome AF: 0.365 AC: 55361 AN: 151750 Hom.: 10303 Cov.: 31 AF XY: 0.359 AC XY: 26611 AN XY: 74148

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.337

Alfa AF: 0.358 Hom.: 16805

Bravo AF: 0.363

Asia WGS AF: 0.320 AC: 1113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.24

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: rs1004446; hg19: chr11-2170143;