rs1140655

Variant names:

• chr12-102397002-A-T
• rs1140655
• NM_000618.5:c.*5505T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001111283.3(IGF1):​c.*5539T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 394,082 control chromosomes in the GnomAD database, including 89,252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (32917 hom., cov: 29)
  • Exomes 𝑓: 0.68 (56335 hom.)
• Consequence: IGF1 NM_001111283.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.836
• Publications: 6 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 12-102397002-A-T is Benign according to our data. Variant chr12-102397002-A-T is described in ClinVar as Benign. ClinVar VariationId is 306840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001111283.3. 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
	IGF1	NM_000618.5	MANE Select	c.*5505T>A		3_prime_UTR	Exon 4 of 4	NP_000609.1
	IGF1	NM_001111283.3		c.*5539T>A		3_prime_UTR	Exon 5 of 5	NP_001104753.1
	IGF1	NM_001414007.1		c.*5505T>A		3_prime_UTR	Exon 5 of 5	NP_001400936.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1	ENST00000337514.11	TSL:1 MANE Select	c.*5505T>A		3_prime_UTR	Exon 4 of 4	ENSP00000337612.7
	HELLPAR	ENST00000626826.1	TSL:6	n.199418A>T		non_coding_transcript_exon	Exon 1 of 1
	LINC02456	ENST00000635615.1	TSL:5	n.450-26069A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99278 AN: 151652 Hom.: 32912 Cov.: 29

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.635

GnomAD4 exome AF: 0.678 AC: 164310 AN: 242312 Hom.: 56335 Cov.: 0 AF XY: 0.678 AC XY: 83362 AN XY: 122872

African (AFR) AF: 0.554 AC: 3919 AN: 7074

American (AMR) AF: 0.660 AC: 4845 AN: 7338

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 5903 AN: 9094

East Asian (EAS) AF: 0.512 AC: 11602 AN: 22670

South Asian (SAS) AF: 0.705 AC: 1791 AN: 2542

European-Finnish (FIN) AF: 0.776 AC: 15821 AN: 20388

Middle Eastern (MID) AF: 0.621 AC: 786 AN: 1266

European-Non Finnish (NFE) AF: 0.700 AC: 109064 AN: 155834

Other (OTH) AF: 0.657 AC: 10579 AN: 16106

GnomAD4 genome AF: 0.654 AC: 99316 AN: 151770 Hom.: 32917 Cov.: 29 AF XY: 0.658 AC XY: 48762 AN XY: 74156

African (AFR) AF: 0.549 AC: 22710 AN: 41332

American (AMR) AF: 0.662 AC: 10105 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2251 AN: 3464

East Asian (EAS) AF: 0.538 AC: 2776 AN: 5156

South Asian (SAS) AF: 0.683 AC: 3282 AN: 4802

European-Finnish (FIN) AF: 0.788 AC: 8300 AN: 10532

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.702 AC: 47681 AN: 67902

Other (OTH) AF: 0.630 AC: 1329 AN: 2110

Alfa AF: 0.680 Hom.: 4433

Bravo AF: 0.636

Asia WGS AF: 0.575 AC: 2001 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Growth delay due to insulin-like growth factor type 1 deficiency (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.81
DANN	Benign	0.80
PhyloP100		0.84
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: rs1140655; hg19: chr12-102790780;