NM_000618.5:c.*5716_*5718delAAA

Variant names:

• chr12-102396788-CTTT-C
• rs200146786
• NM_000618.5:c.*5716_*5718delAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000618.5(IGF1):​c.*5716_*5718delAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000847 in 377,684 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000021 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: IGF1 NM_000618.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161
• Publications: 0 publications found

Genes affected

IGF1 (HGNC:5464): (insulin like growth factor 1) The protein encoded by this gene is similar to insulin in function and structure and is a member of a family of proteins involved in mediating growth and development. The encoded protein is processed from a precursor, bound by a specific receptor, and secreted. Defects in this gene are a cause of insulin-like growth factor I deficiency. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar processing to generate mature protein. [provided by RefSeq, Sep 2015]

HELLPAR (HGNC:43984): (HELLP associated long non-coding RNA)

LINC02456 (HGNC:53389): (long intergenic non-protein coding RNA 2456)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000618.5. 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
	IGF1	NM_000618.5	MANE Select	c.*5716_*5718delAAA		3_prime_UTR	Exon 4 of 4	NP_000609.1	Q5U743
	IGF1	NM_001111283.3		c.*5750_*5752delAAA		3_prime_UTR	Exon 5 of 5	NP_001104753.1	P05019-4
	IGF1	NM_001414007.1		c.*5716_*5718delAAA		3_prime_UTR	Exon 5 of 5	NP_001400936.1	Q5U743

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1	ENST00000337514.11	TSL:1 MANE Select	c.*5716_*5718delAAA		3_prime_UTR	Exon 4 of 4	ENSP00000337612.7	P05019-2
	HELLPAR	ENST00000626826.1	TSL:6	n.199215_199217delTTT		non_coding_transcript_exon	Exon 1 of 1
	LINC02456	ENST00000635615.1	TSL:5	n.450-26272_450-26270delTTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000208 AC: 3 AN: 144206 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000254

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000112

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000153

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000124 AC: 29 AN: 233478 Hom.: 0 AF XY: 0.000127 AC XY: 15 AN XY: 118402

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000294 AC: 2 AN: 6806

American (AMR) AF: 0.000141 AC: 1 AN: 7094

Ashkenazi Jewish (ASJ) AF: 0.000228 AC: 2 AN: 8782

East Asian (EAS) AF: 0.00 AC: 0 AN: 21992

South Asian (SAS) AF: 0.000706 AC: 2 AN: 2834

European-Finnish (FIN) AF: 0.000308 AC: 6 AN: 19498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1208

European-Non Finnish (NFE) AF: 0.000107 AC: 16 AN: 149710

Other (OTH) AF: 0.00 AC: 0 AN: 15554

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000208 AC: 3 AN: 144206 Hom.: 0 Cov.: 31 AF XY: 0.0000143 AC XY: 1 AN XY: 70096

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000254 AC: 1 AN: 39322

American (AMR) AF: 0.00 AC: 0 AN: 14428

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3354

East Asian (EAS) AF: 0.00 AC: 0 AN: 5034

South Asian (SAS) AF: 0.00 AC: 0 AN: 4574

European-Finnish (FIN) AF: 0.000112 AC: 1 AN: 8924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 296

European-Non Finnish (NFE) AF: 0.0000153 AC: 1 AN: 65434

Other (OTH) AF: 0.00 AC: 0 AN: 1954

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.16

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: rs200146786; hg19: chr12-102790566;