chrX-131288648-G-T

Variant names:

• chrX-131288648-G-T
• rs4073307
• NM_001555.5:c.-68+566C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001555.5(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 NM_001555.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• 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=-0.85).
• 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 rank	MANE	Protein	UniProt
IGSF1	NM_001555.5	c.-68+566C>A		intron_variant	Intron 1 of 19	ENST00000361420.8	NP_001546.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGSF1	ENST00000361420.8	c.-68+566C>A		intron_variant	Intron 1 of 19	1	NM_001555.5	ENSP00000355010.3

Frequencies

GnomAD3 genomes AF: 0.205 AC: 22662 AN: 110359 Hom.: 1807 Cov.: 22

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

African (AFR) AF: 0.268 AC: 8121 AN: 30259

American (AMR) AF: 0.141 AC: 1469 AN: 10428

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 565 AN: 2629

East Asian (EAS) AF: 0.267 AC: 924 AN: 3463

South Asian (SAS) AF: 0.282 AC: 718 AN: 2547

European-Finnish (FIN) AF: 0.139 AC: 830 AN: 5954

Middle Eastern (MID) AF: 0.245 AC: 52 AN: 212

European-Non Finnish (NFE) AF: 0.181 AC: 9550 AN: 52742

Other (OTH) AF: 0.218 AC: 328 AN: 1502

Alfa AF: 0.189 Hom.: 13665

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
PhyloP100		-1.3
PromoterAI		-0.0074	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4073307; hg19: chrX-130422622;