rs35587190

chr16-1793899-G-Achr16-1793899-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGFALS	NR_027389.1	n.70+940C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGFALS	ENST00000568221.1	c.48+940C>T		intron_variant		4

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

Gnomad4 AFR exome AF: 0.460

Gnomad4 AMR exome AF: 0.0774

Gnomad4 ASJ exome AF: 0.0840

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.0681

Gnomad4 NFE exome AF: 0.0913

Gnomad4 OTH exome AF: 0.129

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

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.0790

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.0689

Gnomad4 NFE AF: 0.0994

Gnomad4 OTH AF: 0.183

Alfa AF: 0.113 Hom.: 333

Bravo AF: 0.218

Asia WGS AF: 0.272 AC: 943 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	6.4
Dann	Benign	0.42

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;