rs4073307

Positions:

• chrX-131288648-G-T

Variant summary

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

The ENST00000361420.8(IGSF1):​c.-68+566C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 110,412 control chromosomes in the GnomAD database, including 1,811 homozygotes. There are 6,409 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 0.21 (1811 hom., 6409 hem., cov: 22)
• Consequence: IGSF1 ENST00000361420.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF1	NM_001555.5	c.-68+566C>A		intron_variant		ENST00000361420.8	NP_001546.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF1	ENST00000361420.8	c.-68+566C>A		intron_variant		1	NM_001555.5	ENSP00000355010	P4

Frequencies

GnomAD3 genomes AF: 0.205 AC: 22662 AN: 110359 Hom.: 1807 Cov.: 22 AF XY: 0.196 AC XY: 6391 AN XY: 32661

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.205 AC: 22680 AN: 110412 Hom.: 1811 Cov.: 22 AF XY: 0.196 AC XY: 6409 AN XY: 32724

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.218

Alfa AF: 0.187 Hom.: 9574

Bravo AF: 0.211

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.34
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4073307; hg19: chrX-130422622;