GeneBe

chr2-216694521-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_000599.4(IGFBP5):​c.255C>T​(p.Asp85Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

IGFBP5
NM_000599.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.510

Publications

0 publications found
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]
TESHL (HGNC:52740): (testicular germ cell expressed HSF2 interacting lncRNA)
IGFBP-AS1 (HGNC:55655): (IGFBP5 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP7
Synonymous conserved (PhyloP=0.51 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IGFBP5NM_000599.4 linkc.255C>T p.Asp85Asp synonymous_variant Exon 1 of 4 ENST00000233813.5 NP_000590.1 P24593
IGFBP-AS1NR_187138.1 linkn.76G>A non_coding_transcript_exon_variant Exon 1 of 6
IGFBP-AS1NR_187139.1 linkn.76G>A non_coding_transcript_exon_variant Exon 1 of 5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IGFBP5ENST00000233813.5 linkc.255C>T p.Asp85Asp synonymous_variant Exon 1 of 4 1 NM_000599.4 ENSP00000233813.4 P24593

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.98e-7
AC:
1
AN:
1432450
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
710328
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
32516
American (AMR)
AF:
0.00
AC:
0
AN:
40396
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25276
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38422
South Asian (SAS)
AF:
0.00
AC:
0
AN:
82024
European-Finnish (FIN)
AF:
0.0000208
AC:
1
AN:
48098
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5720
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1100682
Other (OTH)
AF:
0.00
AC:
0
AN:
59316
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.36
CADD
Benign
17
DANN
Benign
0.97
PhyloP100
0.51
PromoterAI
-0.027
Neutral
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs1335844350; hg19: chr2-217559244; API