NM_000618.5:c.*263T>A

Variant names:

• chr12-102402244-A-T
• rs70961704
• NM_000618.5:c.*263T>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.*263T>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 0.027 in 227,346 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (60 hom., cov: 32)
  • Exomes 𝑓: 0.026 (33 hom.)
• Consequence: IGF1 NM_000618.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.577
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 12-102402244-A-T is Benign according to our data. Variant chr12-102402244-A-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 306905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0531 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.*263T>A		3_prime_UTR	Exon 4 of 4	NP_000609.1	Q5U743
	IGF1	NM_001111283.3		c.*297T>A		3_prime_UTR	Exon 5 of 5	NP_001104753.1	P05019-4
	IGF1	NM_001414007.1		c.*263T>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.*263T>A		3_prime_UTR	Exon 4 of 4	ENSP00000337612.7	P05019-2
	HELLPAR	ENST00000626826.1	TSL:6	n.204660A>T		non_coding_transcript_exon	Exon 1 of 1
	LINC02456	ENST00000635615.1	TSL:5	n.450-20827A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0274 AC: 4043 AN: 147580 Hom.: 60 Cov.: 32

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.00120

Gnomad AMR AF: 0.0252

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.0173

Gnomad SAS AF: 0.0587

Gnomad FIN AF: 0.0153

Gnomad MID AF: 0.0449

Gnomad NFE AF: 0.0301

Gnomad OTH AF: 0.0270

GnomAD4 exome AF: 0.0262 AC: 2088 AN: 79674 Hom.: 33 Cov.: 0 AF XY: 0.0272 AC XY: 1199 AN XY: 44146

African (AFR) AF: 0.0134 AC: 25 AN: 1872

American (AMR) AF: 0.0284 AC: 114 AN: 4012

Ashkenazi Jewish (ASJ) AF: 0.0495 AC: 103 AN: 2080

East Asian (EAS) AF: 0.0171 AC: 78 AN: 4550

South Asian (SAS) AF: 0.0485 AC: 427 AN: 8806

European-Finnish (FIN) AF: 0.0108 AC: 28 AN: 2596

Middle Eastern (MID) AF: 0.0432 AC: 14 AN: 324

European-Non Finnish (NFE) AF: 0.0232 AC: 1187 AN: 51220

Other (OTH) AF: 0.0266 AC: 112 AN: 4214

GnomAD4 genome AF: 0.0274 AC: 4045 AN: 147672 Hom.: 60 Cov.: 32 AF XY: 0.0261 AC XY: 1882 AN XY: 72004

African (AFR) AF: 0.0201 AC: 812 AN: 40318

American (AMR) AF: 0.0253 AC: 378 AN: 14946

Ashkenazi Jewish (ASJ) AF: 0.0804 AC: 275 AN: 3422

East Asian (EAS) AF: 0.0175 AC: 90 AN: 5142

South Asian (SAS) AF: 0.0587 AC: 278 AN: 4734

European-Finnish (FIN) AF: 0.0153 AC: 142 AN: 9294

Middle Eastern (MID) AF: 0.0414 AC: 12 AN: 290

European-Non Finnish (NFE) AF: 0.0300 AC: 2002 AN: 66642

Other (OTH) AF: 0.0268 AC: 55 AN: 2054

Alfa AF: 0.00380 Hom.: 0

Bravo AF: 0.0273

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Growth delay due to insulin-like growth factor type 1 deficiency (2)
-	-	2	not specified (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.27
DANN	Benign	0.51
PhyloP100		0.58
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: rs70961704; hg19: chr12-102796022;