chrX-131274112-C-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001555.5(IGSF1):c.3846G>C(p.Glu1282Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,209,788 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 43 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00026 ( 0 hom., 10 hem., cov: 23)
Exomes 𝑓: 0.00011 ( 0 hom. 33 hem. )
Consequence
IGSF1
NM_001555.5 missense
NM_001555.5 missense
Scores
1
2
11
Clinical Significance
Conservation
PhyloP100: -0.0410
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.014509708).
BP6
?
Variant X-131274112-C-G is Benign according to our data. Variant chrX-131274112-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3108783.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00026 (29/111666) while in subpopulation NFE AF= 0.0000565 (3/53099). AF 95% confidence interval is 0.000015. There are 0 homozygotes in gnomad4. There are 10 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAd at 10 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IGSF1 | NM_001555.5 | c.3846G>C | p.Glu1282Asp | missense_variant | 19/20 | ENST00000361420.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IGSF1 | ENST00000361420.8 | c.3846G>C | p.Glu1282Asp | missense_variant | 19/20 | 1 | NM_001555.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000260 AC: 29AN: 111666Hom.: 0 Cov.: 23 AF XY: 0.000296 AC XY: 10AN XY: 33814
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000273 AC: 5AN: 183366Hom.: 0 AF XY: 0.0000590 AC XY: 4AN XY: 67816
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GnomAD4 exome AF: 0.000107 AC: 117AN: 1098122Hom.: 0 Cov.: 30 AF XY: 0.0000908 AC XY: 33AN XY: 363478
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GnomAD4 genome ? AF: 0.000260 AC: 29AN: 111666Hom.: 0 Cov.: 23 AF XY: 0.000296 AC XY: 10AN XY: 33814
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 27, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
FATHMM_MKL
Benign
N
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;D;T
Sift4G
Benign
T;T;T;T
Polyphen
P;D;.;P
Vest4
MutPred
0.49
.;Loss of sheet (P = 0.0126);.;.;
MVP
MPC
0.71
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at