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GeneBe

rs6529473

chrX-131274771-G-AchrX-131274771-G-CchrX-131274771-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001555.5(IGSF1):c.3579C>T(p.Val1193=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,208,393 control chromosomes in the GnomAD database, including 34,544 homozygotes. There are 107,036 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 4060 hom., 10057 hem., cov: 22)
Exomes 𝑓: 0.26 ( 30484 hom. 96979 hem. )

Consequence

IGSF1
NM_001555.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.731
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant X-131274771-G-A is Benign according to our data. Variant chrX-131274771-G-A is described in ClinVar as [Benign]. Clinvar id is 257592.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-131274771-G-A is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.731 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IGSF1NM_001555.5 linkuse as main transcriptc.3579C>T p.Val1193= synonymous_variant 18/20 ENST00000361420.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IGSF1ENST00000361420.8 linkuse as main transcriptc.3579C>T p.Val1193= synonymous_variant 18/201 NM_001555.5 P4Q8N6C5-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.299
AC:
33026
AN:
110535
Hom.:
4064
Cov.:
22
AF XY:
0.306
AC XY:
10033
AN XY:
32813
show subpopulations
Gnomad AFR
AF:
0.345
Gnomad AMI
AF:
0.137
Gnomad AMR
AF:
0.416
Gnomad ASJ
AF:
0.250
Gnomad EAS
AF:
0.820
Gnomad SAS
AF:
0.443
Gnomad FIN
AF:
0.235
Gnomad MID
AF:
0.241
Gnomad NFE
AF:
0.219
Gnomad OTH
AF:
0.313
GnomAD3 exomes
AF:
0.350
AC:
64209
AN:
183457
Hom.:
9446
AF XY:
0.337
AC XY:
22855
AN XY:
67895
show subpopulations
Gnomad AFR exome
AF:
0.350
Gnomad AMR exome
AF:
0.527
Gnomad ASJ exome
AF:
0.259
Gnomad EAS exome
AF:
0.827
Gnomad SAS exome
AF:
0.431
Gnomad FIN exome
AF:
0.243
Gnomad NFE exome
AF:
0.223
Gnomad OTH exome
AF:
0.309
GnomAD4 exome
AF:
0.263
AC:
289224
AN:
1097802
Hom.:
30484
Cov.:
33
AF XY:
0.267
AC XY:
96979
AN XY:
363248
show subpopulations
Gnomad4 AFR exome
AF:
0.355
Gnomad4 AMR exome
AF:
0.517
Gnomad4 ASJ exome
AF:
0.258
Gnomad4 EAS exome
AF:
0.816
Gnomad4 SAS exome
AF:
0.421
Gnomad4 FIN exome
AF:
0.239
Gnomad4 NFE exome
AF:
0.220
Gnomad4 OTH exome
AF:
0.297
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.299
AC:
33037
AN:
110591
Hom.:
4060
Cov.:
22
AF XY:
0.306
AC XY:
10057
AN XY:
32879
show subpopulations
Gnomad4 AFR
AF:
0.345
Gnomad4 AMR
AF:
0.415
Gnomad4 ASJ
AF:
0.250
Gnomad4 EAS
AF:
0.821
Gnomad4 SAS
AF:
0.443
Gnomad4 FIN
AF:
0.235
Gnomad4 NFE
AF:
0.219
Gnomad4 OTH
AF:
0.315
Alfa
AF:
0.248
Hom.:
13562
Bravo
AF:
0.323
EpiCase
AF:
0.222
EpiControl
AF:
0.225

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxNov 12, 2018- -
X-linked central congenital hypothyroidism with late-onset testicular enlargement Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabAug 10, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
Cadd
Benign
14
Dann
Benign
0.63

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.31
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.31
Position offset: -5

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs6529473; hg19: chrX-130408745; COSMIC: COSV63838020; COSMIC: COSV63838020; API