chr7-23443066-G-A

Variant names:

• chr7-23443066-G-A
• rs6957923
• NM_006547.3:c.237-24242C>T

Variant summary

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

The NM_006547.3(IGF2BP3):​c.237-24242C>T 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 146,114 control chromosomes in the GnomAD database, including 9,369 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 (9369 hom., cov: 28)
• Consequence: IGF2BP3 NM_006547.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.557
• Publications: 15 publications found

Genes affected

IGF2BP3 (HGNC:28868): (insulin like growth factor 2 mRNA binding protein 3) The protein encoded by this gene is primarily found in the nucleolus, where it can bind to the 5' UTR of the insulin-like growth factor II leader 3 mRNA and may repress translation of insulin-like growth factor II during late development. The encoded protein contains several KH domains, which are important in RNA binding and are known to be involved in RNA synthesis and metabolism. A pseudogene exists on chromosome 7, and there are putative pseudogenes on other chromosomes. [provided by RefSeq, Jul 2008]

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 (AFR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006547.3. 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
	IGF2BP3	NM_006547.3	MANE Select	c.237-24242C>T		intron	N/A	NP_006538.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2BP3	ENST00000258729.8	TSL:1 MANE Select	c.237-24242C>T		intron	N/A	ENSP00000258729.3	O00425-1
	IGF2BP3	ENST00000922496.1		c.237-24242C>T		intron	N/A	ENSP00000592555.1
	IGF2BP3	ENST00000421467.6	TSL:5	n.236+25416C>T		intron	N/A	ENSP00000395936.1	F8WD15

Frequencies

GnomAD3 genomes AF: 0.355 AC: 51871 AN: 146044 Hom.: 9367 Cov.: 28

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.0559

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.419

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.355 AC: 51910 AN: 146114 Hom.: 9369 Cov.: 28 AF XY: 0.348 AC XY: 24589 AN XY: 70712

African (AFR) AF: 0.401 AC: 15864 AN: 39530

American (AMR) AF: 0.302 AC: 4374 AN: 14466

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1146 AN: 3448

East Asian (EAS) AF: 0.0560 AC: 271 AN: 4836

South Asian (SAS) AF: 0.341 AC: 1585 AN: 4652

European-Finnish (FIN) AF: 0.266 AC: 2363 AN: 8876

Middle Eastern (MID) AF: 0.429 AC: 120 AN: 280

European-Non Finnish (NFE) AF: 0.377 AC: 25290 AN: 67118

Other (OTH) AF: 0.382 AC: 774 AN: 2028

Alfa AF: 0.352 Hom.: 14795

Bravo AF: 0.349

Asia WGS AF: 0.204 AC: 714 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.30
DANN	Benign	0.48
PhyloP100		-0.56
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: rs6957923; hg19: chr7-23482685; COSMIC: COSV51681984;