rs10521767

Variant names:

• chrX-131322577-T-C
• rs10521767
• ENST00000370904.6:c.-288-18454A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

IGSF1 Gene-Disease associations (from GenCC):

• X-linked central congenital hypothyroidism with late-onset testicular enlargement

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000287806 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGSF1	ENST00000370904.6	c.-288-18454A>G		intron_variant	Intron 6 of 26	2		ENSP00000359941.1
ENSG00000287806	ENST00000773800.1	n.561-52810T>C		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.106 AC: 11828 AN: 111807 Hom.: 491 Cov.: 23

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

African (AFR) AF: 0.0847 AC: 2611 AN: 30842

American (AMR) AF: 0.0683 AC: 723 AN: 10583

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 382 AN: 2638

East Asian (EAS) AF: 0.119 AC: 422 AN: 3540

South Asian (SAS) AF: 0.114 AC: 307 AN: 2693

European-Finnish (FIN) AF: 0.107 AC: 648 AN: 6064

Middle Eastern (MID) AF: 0.144 AC: 31 AN: 215

European-Non Finnish (NFE) AF: 0.122 AC: 6453 AN: 53076

Other (OTH) AF: 0.105 AC: 161 AN: 1527

Alfa AF: 0.116 Hom.: 2519

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
PhyloP100		0.053
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: rs10521767; hg19: chrX-130456551;