X-131273901-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_001555.5(IGSF1):c.3906C>G(p.Thr1302=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0003 in 1,208,539 control chromosomes in the GnomAD database, including 1 homozygotes. There are 98 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., 53 hem., cov: 22)
  • Exomes 𝑓: 0.00017 (1 hom. 45 hem.)
• Consequence: IGSF1 NM_001555.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:2
• Conservation: PhyloP100: 0.362

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant X-131273901-G-C is Benign according to our data. Variant chrX-131273901-G-C is described in ClinVar as [Benign]. Clinvar id is 1284299.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-131273901-G-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.362 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00154 (172/111469) while in subpopulation AFR AF= 0.00536 (164/30614). AF 95% confidence interval is 0.00469. There are 0 homozygotes in gnomad4. There are 53 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 53 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGSF1	NM_001555.5	c.3906C>G	p.Thr1302=	synonymous_variant	20/20	ENST00000361420.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGSF1	ENST00000361420.8	c.3906C>G	p.Thr1302=	synonymous_variant	20/20	1	NM_001555.5	P4

Frequencies

GnomAD3 genomes AF: 0.00154 AC: 172 AN: 111413 Hom.: 0 Cov.: 22 AF XY: 0.00158 AC XY: 53 AN XY: 33595

Gnomad AFR AF: 0.00537

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000566

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00134

GnomAD3 exomes AF: 0.000514 AC: 94 AN: 182883 Hom.: 1 AF XY: 0.000371 AC XY: 25 AN XY: 67357

Gnomad AFR exome AF: 0.00631

Gnomad AMR exome AF: 0.000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.000173 AC: 190 AN: 1097070 Hom.: 1 Cov.: 30 AF XY: 0.000124 AC XY: 45 AN XY: 362452

Gnomad4 AFR exome AF: 0.00614

Gnomad4 AMR exome AF: 0.000341

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.000326

GnomAD4 genome AF: 0.00154 AC: 172 AN: 111469 Hom.: 0 Cov.: 22 AF XY: 0.00157 AC XY: 53 AN XY: 33661

Gnomad4 AFR AF: 0.00536

Gnomad4 AMR AF: 0.000565

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00133

Alfa AF: 0.000781 Hom.: 4

Bravo AF: 0.00171

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	3.5
Dann	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs150776874; hg19: chrX-130407875;