rs3842754

Positions:

• chr11-2159615-G-A
• chr11-2159615-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001042376.3(INS-IGF2):​c.187+1170C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,124 control chromosomes in the GnomAD database, including 2,128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.15 (2128 hom., cov: 32)
• Consequence: INS-IGF2 NM_001042376.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.39

Genes affected

INS-IGF2 (HGNC:33527): (INS-IGF2 readthrough) This locus includes two alternatively spliced read-through transcript variants which align to the INS gene in the 5' region and to the IGF2 gene in the 3' region. One transcript is predicted to encode a protein which shares the N-terminus with the INS protein but has a distinct and longer C-terminus, whereas the other transcript is a candidate for nonsense-mediated decay (NMD). The transcripts are imprinted and are paternally expressed in the limb and eye. [provided by RefSeq, Jul 2008]

INS-IGF2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 11-2159615-G-A is Benign according to our data. Variant chr11-2159615-G-A is described in ClinVar as [Benign]. Clinvar id is 1265784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INS-IGF2	NM_001042376.3	c.187+1170C>T		intron_variant			NP_001035835.1
INS-IGF2	NR_003512.4	n.246+1170C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INS-IGF2	ENST00000397270.1	c.187+1170C>T		intron_variant		1		ENSP00000380440.1
INS-IGF2	ENST00000356578.8	n.187+1170C>T		intron_variant		5		ENSP00000348986.4

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22649 AN: 152006 Hom.: 2128 Cov.: 32

Gnomad AFR AF: 0.0399

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.0413

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.149 AC: 22644 AN: 152124 Hom.: 2128 Cov.: 32 AF XY: 0.144 AC XY: 10717 AN XY: 74358

Gnomad4 AFR AF: 0.0398

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.0412

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.129

Alfa AF: 0.102 Hom.: 154

Bravo AF: 0.143

Asia WGS AF: 0.0910 AC: 316 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 25, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.68
DANN	Benign	0.65

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: rs3842754; hg19: chr11-2180845;