Variant 2-216694726-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000233813.5(IGFBP5):c.50C>G(p.Pro17Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,306,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

IGFBP5
ENST00000233813.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.733

Variant links:

Genes affected

IGFBP5 (HGNC:5474): (insulin like growth factor binding protein 5) Enables insulin-like growth factor I binding activity. Involved in several processes, including cellular response to cAMP; regulation of smooth muscle cell migration; and regulation of smooth muscle cell proliferation. Part of insulin-like growth factor ternary complex. Biomarker of pulmonary fibrosis. [provided by Alliance of Genome Resources, Apr 2022]

IGFBP5 links:

DIRC3-AS1 (HGNC:50636): (DIRC3 antisense RNA 1)

DIRC3-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05333048).

BS2

High AC in GnomAdExome4 at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGFBP5	NM_000599.4 linkuse as main transcript	c.50C>G	p.Pro17Arg	missense_variant	1/4	ENST00000233813.5	NP_000590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGFBP5	ENST00000233813.5 linkuse as main transcript	c.50C>G	p.Pro17Arg	missense_variant	1/4	1	NM_000599.4	ENSP00000233813	P1
DIRC3-AS1	ENST00000695932.1 linkuse as main transcript	n.323G>C		non_coding_transcript_exon_variant	1/12

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000110

AC:

AN:

90574

Hom.:

AF XY:

0.0000201

AC XY:

AN XY:

49816

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000139

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000199

AC:

AN:

1306632

Hom.:

Cov.:

AF XY:

0.0000251

AC XY:

AN XY:

636808

show subpopulations

Gnomad4 AFR exome

AF:

0.0000384

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000160

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000221

Gnomad4 OTH exome

AF:

0.0000186

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000864

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2024

The c.50C>G (p.P17R) alteration is located in exon 1 (coding exon 1) of the IGFBP5 gene. This alteration results from a C to G substitution at nucleotide position 50, causing the proline (P) at amino acid position 17 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.17

T;.

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.51

T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.053

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.40

N;.

MutationTaster

Benign

0.95

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.64

N;N

REVEL

Benign

0.034

Sift

Benign

0.53

T;T

Sift4G

Benign

0.41

T;T

Polyphen

0.0

B;.

Vest4

0.097

MVP

0.14

MPC

0.67

ClinPred

0.031

GERP RS

3.6

Varity_R

0.048

gMVP

0.35

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over