chr12-102396074-C-G

Variant names:

• chr12-102396074-C-G
• rs5742714
• NM_000618.5:c.*6433G>C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_000618.5(IGF1):​c.*6433G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0904 in 152,114 control chromosomes in the GnomAD database, including 652 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.090 (652 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: IGF1 NM_000618.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.57
• Publications: 36 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 12-102396074-C-G is Benign according to our data. Variant chr12-102396074-C-G is described in ClinVar as Benign. ClinVar VariationId is 306830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

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.*6433G>C		3_prime_UTR	Exon 4 of 4	NP_000609.1	Q5U743
	IGF1	NM_001111283.3		c.*6467G>C		3_prime_UTR	Exon 5 of 5	NP_001104753.1	P05019-4
	IGF1	NM_001414007.1		c.*6433G>C		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.*6433G>C		3_prime_UTR	Exon 4 of 4	ENSP00000337612.7	P05019-2
	HELLPAR	ENST00000626826.1	TSL:6	n.198490C>G		non_coding_transcript_exon	Exon 1 of 1
	LINC02456	ENST00000635615.1	TSL:5	n.450-26997C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0904 AC: 13739 AN: 151996 Hom.: 650 Cov.: 32

Gnomad AFR AF: 0.0848

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.0620

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0610

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0956

Gnomad OTH AF: 0.0923

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0904 AC: 13750 AN: 152114 Hom.: 652 Cov.: 32 AF XY: 0.0880 AC XY: 6542 AN XY: 74348

African (AFR) AF: 0.0848 AC: 3518 AN: 41490

American (AMR) AF: 0.0619 AC: 947 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 478 AN: 3470

East Asian (EAS) AF: 0.167 AC: 865 AN: 5172

South Asian (SAS) AF: 0.111 AC: 536 AN: 4822

European-Finnish (FIN) AF: 0.0610 AC: 645 AN: 10576

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0956 AC: 6499 AN: 67980

Other (OTH) AF: 0.0942 AC: 199 AN: 2112

Alfa AF: 0.0883 Hom.: 99

Bravo AF: 0.0908

Asia WGS AF: 0.145 AC: 502 AN: 3470

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	-0.43
CADD	Benign	15
DANN	Benign	0.78
PhyloP100		1.6
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: rs5742714; hg19: chr12-102789852;