rs10521770

Variant names:

• chrX-131565100-G-A
• rs10521770
• ENST00000370904.6:c.-913+13568C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000370904.6(IGSF1):​c.-913+13568C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 111,505 control chromosomes in the GnomAD database, including 10 homozygotes. There are 404 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 0.014 (10 hom., 404 hem., cov: 23)
• Consequence: IGSF1 ENST00000370904.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679
• Publications: 0 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0143 (1598/111505) while in subpopulation NFE AF = 0.0241 (1275/52981). AF 95% confidence interval is 0.023. There are 10 homozygotes in GnomAd4. There are 404 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 XL gene

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.-913+13568C>T		intron_variant	Intron 1 of 26	2		ENSP00000359941.1

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 1597 AN: 111451 Hom.: 10 Cov.: 23

Gnomad AFR AF: 0.00283

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.00316

Gnomad ASJ AF: 0.00454

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00635

Gnomad FIN AF: 0.0226

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0240

Gnomad OTH AF: 0.00533

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

GnomAD4 genome AF: 0.0143 AC: 1598 AN: 111505 Hom.: 10 Cov.: 23 AF XY: 0.0120 AC XY: 404 AN XY: 33719

African (AFR) AF: 0.00283 AC: 87 AN: 30770

American (AMR) AF: 0.00316 AC: 33 AN: 10451

Ashkenazi Jewish (ASJ) AF: 0.00454 AC: 12 AN: 2641

East Asian (EAS) AF: 0.00 AC: 0 AN: 3559

South Asian (SAS) AF: 0.00637 AC: 17 AN: 2668

European-Finnish (FIN) AF: 0.0226 AC: 136 AN: 6015

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.0241 AC: 1275 AN: 52981

Other (OTH) AF: 0.00526 AC: 8 AN: 1520

Alfa AF: 0.0224 Hom.: 118

Bravo AF: 0.0124

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.15
DANN	Benign	0.60
PhyloP100		-0.68

Splicing

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

Other links and lift over

dbSNP: rs10521770; hg19: chrX-130699074;