X-131274457-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001555.5(IGSF1):c.3751+142A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.67 (18042 hom., 22042 hem., cov: 22)
  • Exomes 𝑓: 0.60 (77300 hom. 101797 hem.)
  • Failed GnomAD Quality Control
• Consequence: IGSF1 NM_001555.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.13

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant X-131274457-T-C is Benign according to our data. Variant chrX-131274457-T-C is described in ClinVar as [Benign]. Clinvar id is 1272197.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-131274457-T-C is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAd at 18036 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGSF1	NM_001555.5	c.3751+142A>G		intron_variant		ENST00000361420.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGSF1	ENST00000361420.8	c.3751+142A>G		intron_variant		1	NM_001555.5	P4

Frequencies

GnomAD3 genomes AF: 0.670 AC: 74062 AN: 110590 Hom.: 18036 Cov.: 22 AF XY: 0.670 AC XY: 21989 AN XY: 32826

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.683

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.605 AC: 354506 AN: 586253 Hom.: 77300 AF XY: 0.617 AC XY: 101797 AN XY: 165077

Gnomad4 AFR exome AF: 0.833

Gnomad4 AMR exome AF: 0.814

Gnomad4 ASJ exome AF: 0.650

Gnomad4 EAS exome AF: 0.818

Gnomad4 SAS exome AF: 0.584

Gnomad4 FIN exome AF: 0.584

Gnomad4 NFE exome AF: 0.574

Gnomad4 OTH exome AF: 0.627

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.670 AC: 74119 AN: 110644 Hom.: 18042 Cov.: 22 AF XY: 0.670 AC XY: 22042 AN XY: 32890

Gnomad4 AFR AF: 0.823

Gnomad4 AMR AF: 0.770

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.825

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.572

Gnomad4 OTH AF: 0.682

Alfa AF: 0.595 Hom.: 62879

Bravo AF: 0.698

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	8.7
Dann	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs6418944; hg19: chrX-130408431;