rs10521770

Positions:

• chrX-131565100-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGSF1	ENST00000370904.6	c.-913+13568C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 1597 AN: 111451 Hom.: 10 Cov.: 23 AF XY: 0.0120 AC XY: 404 AN XY: 33655

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

Gnomad4 AFR AF: 0.00283

Gnomad4 AMR AF: 0.00316

Gnomad4 ASJ AF: 0.00454

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00637

Gnomad4 FIN AF: 0.0226

Gnomad4 NFE AF: 0.0241

Gnomad4 OTH AF: 0.00526

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10521770; hg19: chrX-130699074;