rs1388340350

Variant names:

• chr4-57110023-A-G
• rs1388340350
• NM_001553.3:c.329T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001553.3(IGFBP7):​c.329T>C​(p.Val110Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000856 in 1,553,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000090 (0 hom.)
• Consequence: IGFBP7 NM_001553.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13
• Publications: 0 publications found

Genes affected

IGFBP7 (HGNC:5476): (insulin like growth factor binding protein 7) This gene encodes a member of the insulin-like growth factor (IGF)-binding protein (IGFBP) family. IGFBPs bind IGFs with high affinity, and regulate IGF availability in body fluids and tissues and modulate IGF binding to its receptors. This protein binds IGF-I and IGF-II with relatively low affinity, and belongs to a subfamily of low-affinity IGFBPs. It also stimulates prostacyclin production and cell adhesion. Alternatively spliced transcript variants encoding different isoforms have been described for this gene, and one variant has been associated with retinal arterial macroaneurysm (PMID:21835307). [provided by RefSeq, Dec 2011]

IGFBP7-AS1 (HGNC:40296): (IGFBP7 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24138585).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001553.3. 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
	IGFBP7	NM_001553.3	MANE Select	c.329T>C	p.Val110Ala	missense	Exon 1 of 5	NP_001544.1	Q16270-1
	IGFBP7	NM_001253835.2		c.329T>C	p.Val110Ala	missense	Exon 1 of 4	NP_001240764.1	Q16270-2
	IGFBP7-AS1	NR_034081.1		n.209+53A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP7	ENST00000295666.6	TSL:1 MANE Select	c.329T>C	p.Val110Ala	missense	Exon 1 of 5	ENSP00000295666.4	Q16270-1
	IGFBP7-AS1	ENST00000499667.6	TSL:1	n.209+53A>G		intron	N/A
	IGFBP7	ENST00000896424.1		c.329T>C	p.Val110Ala	missense	Exon 1 of 7	ENSP00000566483.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152018 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000256 AC: 4 AN: 156002 AF XY: 0.0000233

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000626

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000899 AC: 126 AN: 1401718 Hom.: 0 Cov.: 31 AF XY: 0.0000908 AC XY: 63 AN XY: 693646

African (AFR) AF: 0.0000311 AC: 1 AN: 32164

American (AMR) AF: 0.00 AC: 0 AN: 38038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25262

East Asian (EAS) AF: 0.00 AC: 0 AN: 36940

South Asian (SAS) AF: 0.0000249 AC: 2 AN: 80428

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5460

European-Non Finnish (NFE) AF: 0.000108 AC: 117 AN: 1087872

Other (OTH) AF: 0.000103 AC: 6 AN: 58484

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152018 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74260

African (AFR) AF: 0.00 AC: 0 AN: 41402

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67972

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000597 Hom.: 0

Bravo AF: 0.0000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.60	T
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.1
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.051
Sift	Benign	0.049	D
Sift4G	Benign	0.094	T
Polyphen		0.18	B
Vest4		0.19
MutPred		0.48		Loss of sheet (P = 0.0025)
MVP		0.45
MPC		0.82
ClinPred		0.13	T
GERP RS		1.5
PromoterAI		0.046	Neutral
Varity_R		0.10
gMVP		0.57
Mutation Taster		=78/22	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

Other links and lift over

dbSNP: rs1388340350; hg19: chr4-57976189;