chr16-1793899-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000568221.1(IGFALS):​c.48+940C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 416,562 control chromosomes in the GnomAD database, including 7,824 homozygotes. 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: 𝑓 0.21 (5542 hom., cov: 35)
  • Exomes 𝑓: 0.11 (2282 hom.)
• Consequence: IGFALS ENST00000568221.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000568221.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFALS	NR_027389.1		n.70+940C>T		intron	N/A
	IGFALS	NM_004970.3	MANE Select	c.-247C>T		upstream_gene	N/A	NP_004961.1
	IGFALS	NM_001146006.2		c.-247C>T		upstream_gene	N/A	NP_001139478.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFALS	ENST00000568221.1	TSL:4	c.48+940C>T		intron	N/A	ENSP00000456923.1
	IGFALS	ENST00000215539.4	TSL:1 MANE Select	c.-247C>T		upstream_gene	N/A	ENSP00000215539.3
	IGFALS	ENST00000415638.3	TSL:2	c.-247C>T		upstream_gene	N/A	ENSP00000416683.3

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31735 AN: 152022 Hom.: 5517 Cov.: 35

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0790

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.0689

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0994

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.109 AC: 28691 AN: 264422 Hom.: 2282 AF XY: 0.110 AC XY: 15045 AN XY: 136272

African (AFR) AF: 0.460 AC: 3235 AN: 7036

American (AMR) AF: 0.0774 AC: 706 AN: 9120

Ashkenazi Jewish (ASJ) AF: 0.0840 AC: 789 AN: 9388

East Asian (EAS) AF: 0.113 AC: 2655 AN: 23516

South Asian (SAS) AF: 0.233 AC: 2433 AN: 10424

European-Finnish (FIN) AF: 0.0681 AC: 1421 AN: 20852

Middle Eastern (MID) AF: 0.107 AC: 140 AN: 1304

European-Non Finnish (NFE) AF: 0.0913 AC: 15145 AN: 165964

Other (OTH) AF: 0.129 AC: 2167 AN: 16818

GnomAD4 genome AF: 0.209 AC: 31814 AN: 152140 Hom.: 5542 Cov.: 35 AF XY: 0.206 AC XY: 15328 AN XY: 74388

African (AFR) AF: 0.473 AC: 19641 AN: 41494

American (AMR) AF: 0.110 AC: 1687 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0790 AC: 274 AN: 3470

East Asian (EAS) AF: 0.145 AC: 748 AN: 5160

South Asian (SAS) AF: 0.311 AC: 1503 AN: 4828

European-Finnish (FIN) AF: 0.0689 AC: 732 AN: 10618

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0994 AC: 6755 AN: 67954

Other (OTH) AF: 0.183 AC: 386 AN: 2110

Alfa AF: 0.127 Hom.: 411

Bravo AF: 0.218

Asia WGS AF: 0.272 AC: 943 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.4
DANN	Benign	0.42
PhyloP100		-0.28
PromoterAI		-0.023	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs35587190; hg19: chr16-1843900;