ENST00000568221.1:c.48+940C>G

Variant names:

• chr16-1793899-G-C
• rs35587190
• ENST00000568221.1:c.48+940C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000568221.1(IGFALS):​c.48+940C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 35)
• Consequence: IGFALS ENST00000568221.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276

Genes affected

IGFALS (HGNC:5468): (insulin like growth factor binding protein acid labile subunit) The protein encoded by this gene is a serum protein that binds insulin-like growth factors, increasing their half-life and their vascular localization. Production of the encoded protein, which contains twenty leucine-rich repeats, is stimulated by growth hormone. Defects in this gene are a cause of acid-labile subunit deficiency, which maifests itself in a delayed and slow puberty. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

SPSB3 (HGNC:30629): (splA/ryanodine receptor domain and SOCS box containing 3) Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Predicted to be located in cytosol. Predicted to be part of SCF ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFALS	NR_027389.1	n.70+940C>G		intron_variant	Intron 1 of 1
IGFALS	NM_004970.3	c.-247C>G		upstream_gene_variant		ENST00000215539.4	NP_004961.1
IGFALS	NM_001146006.2	c.-247C>G		upstream_gene_variant			NP_001139478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFALS	ENST00000568221.1	c.48+940C>G		intron_variant	Intron 1 of 1	4		ENSP00000456923.1
IGFALS	ENST00000215539.4	c.-247C>G		upstream_gene_variant		1	NM_004970.3	ENSP00000215539.3
IGFALS	ENST00000415638.3	c.-247C>G		upstream_gene_variant		2		ENSP00000416683.3
SPSB3	ENST00000569769.1	c.-275C>G		upstream_gene_variant		3		ENSP00000455098.1

Frequencies

GnomAD3 genomes Cov.: 35

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.36

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs35587190; hg19: chr16-1843900;