NM_000618.5:c.*6093G>A

Variant names:

• chr12-102396414-C-T
• rs6219
• NM_000618.5:c.*6093G>A

Variant summary

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

The NM_000618.5(IGF1):​c.*6093G>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 0.0905 in 153,244 control chromosomes in the GnomAD database, including 662 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.090 (655 hom., cov: 32)
  • Exomes 𝑓: 0.10 (7 hom.)
• Consequence: IGF1 NM_000618.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0480
• Publications: 28 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=-0.82).
• BP6: Variant 12-102396414-C-T is Benign according to our data. Variant chr12-102396414-C-T is described in ClinVar as Benign. ClinVar VariationId is 306836.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.*6093G>A		3_prime_UTR	Exon 4 of 4	NP_000609.1	Q5U743
	IGF1	NM_001111283.3		c.*6127G>A		3_prime_UTR	Exon 5 of 5	NP_001104753.1	P05019-4
	IGF1	NM_001414007.1		c.*6093G>A		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.*6093G>A		3_prime_UTR	Exon 4 of 4	ENSP00000337612.7	P05019-2
	HELLPAR	ENST00000626826.1	TSL:6	n.198830C>T		non_coding_transcript_exon	Exon 1 of 1
	LINC02456	ENST00000635615.1	TSL:5	n.450-26657C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0904 AC: 13748 AN: 152038 Hom.: 653 Cov.: 32

Gnomad AFR AF: 0.0848

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.0619

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0611

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0956

Gnomad OTH AF: 0.0923

GnomAD4 exome AF: 0.100 AC: 109 AN: 1088 Hom.: 7 Cov.: 0 AF XY: 0.101 AC XY: 54 AN XY: 534

African (AFR) AF: 0.0676 AC: 5 AN: 74

American (AMR) AF: 0.00 AC: 0 AN: 28

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 7 AN: 46

East Asian (EAS) AF: 0.212 AC: 14 AN: 66

South Asian (SAS) AF: 0.00 AC: 0 AN: 8

European-Finnish (FIN) AF: 0.107 AC: 3 AN: 28

Middle Eastern (MID) AF: 0.375 AC: 3 AN: 8

European-Non Finnish (NFE) AF: 0.0894 AC: 66 AN: 738

Other (OTH) AF: 0.120 AC: 11 AN: 92

GnomAD4 genome AF: 0.0904 AC: 13759 AN: 152156 Hom.: 655 Cov.: 32 AF XY: 0.0880 AC XY: 6547 AN XY: 74376

African (AFR) AF: 0.0848 AC: 3518 AN: 41508

American (AMR) AF: 0.0619 AC: 945 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 479 AN: 3468

East Asian (EAS) AF: 0.167 AC: 866 AN: 5176

South Asian (SAS) AF: 0.111 AC: 537 AN: 4822

European-Finnish (FIN) AF: 0.0611 AC: 647 AN: 10594

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

European-Non Finnish (NFE) AF: 0.0957 AC: 6505 AN: 67992

Other (OTH) AF: 0.0941 AC: 199 AN: 2114

Alfa AF: 0.0953 Hom.: 1291

Bravo AF: 0.0908

Asia WGS AF: 0.146 AC: 508 AN: 3478

ClinVar

ClinVar submissions

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	-0.82
CADD	Benign	9.2
DANN	Benign	0.72
PhyloP100		-0.048
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: rs6219; hg19: chr12-102790192;