rs10521767

Positions:

• chrX-131322577-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000370904.6(IGSF1):​c.-288-18454A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 111,860 control chromosomes in the GnomAD database, including 490 homozygotes. There are 3,452 hemizygotes in GnomAD. 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 0.11 (490 hom., 3452 hem., cov: 23)
• Consequence: IGSF1 ENST00000370904.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530

Genes affected

IGSF1 (HGNC:5948): (immunoglobulin superfamily member 1) This gene encodes a member of the immunoglobulin-like domain-containing superfamily. Proteins in this superfamily contain varying numbers of immunoglobulin-like domains and are thought to participate in the regulation of interactions between cells. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.131322577T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF1	ENST00000370904.6	c.-288-18454A>G		intron_variant		2		ENSP00000359941.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 11828 AN: 111807 Hom.: 491 Cov.: 23 AF XY: 0.101 AC XY: 3449 AN XY: 34011

Gnomad AFR AF: 0.0847

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0684

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.157

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.106 AC: 11829 AN: 111860 Hom.: 490 Cov.: 23 AF XY: 0.101 AC XY: 3452 AN XY: 34074

Gnomad4 AFR AF: 0.0847

Gnomad4 AMR AF: 0.0683

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.105

Alfa AF: 0.120 Hom.: 2019

Bravo AF: 0.103

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.3
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10521767; hg19: chrX-130456551;