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GeneBe

11-133921271-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001277285.4(IGSF9B):c.2454G>A(p.Ser818=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00619 in 1,611,166 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0047 ( 5 hom., cov: 33)
Exomes 𝑓: 0.0064 ( 37 hom. )

Consequence

IGSF9B
NM_001277285.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.664
Variant links:
Genes affected
IGSF9B (HGNC:32326): (immunoglobulin superfamily member 9B) Predicted to enable kinase binding activity. Predicted to be involved in synaptic membrane adhesion. Predicted to act upstream of or within homophilic cell adhesion via plasma membrane adhesion molecules and positive regulation of inhibitory postsynaptic potential. Predicted to be located in dendrite; inhibitory synapse; and neuronal cell body. Predicted to be active in GABA-ergic synapse; neuron projection; and postsynaptic specialization of symmetric synapse. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 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=-0.65).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-133921271-C-T is Benign according to our data. Variant chr11-133921271-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642551.Status of the report is criteria_provided_single_submitter, 1 stars.
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=-0.664 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 5 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IGSF9BNM_001277285.4 linkuse as main transcriptc.2454G>A p.Ser818= synonymous_variant 18/20 ENST00000533871.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IGSF9BENST00000533871.8 linkuse as main transcriptc.2454G>A p.Ser818= synonymous_variant 18/205 NM_001277285.4 P1Q9UPX0-2
IGSF9BENST00000321016.12 linkuse as main transcriptc.2454G>A p.Ser818= synonymous_variant 18/195 Q9UPX0-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00468
AC:
713
AN:
152220
Hom.:
5
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00366
Gnomad ASJ
AF:
0.000864
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00923
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00726
Gnomad OTH
AF:
0.00382
GnomAD3 exomes
AF:
0.00422
AC:
1044
AN:
247416
Hom.:
7
AF XY:
0.00441
AC XY:
592
AN XY:
134356
show subpopulations
Gnomad AFR exome
AF:
0.00116
Gnomad AMR exome
AF:
0.00154
Gnomad ASJ exome
AF:
0.000199
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00105
Gnomad FIN exome
AF:
0.00863
Gnomad NFE exome
AF:
0.00658
Gnomad OTH exome
AF:
0.00382
GnomAD4 exome
AF:
0.00635
AC:
9268
AN:
1458828
Hom.:
37
Cov.:
34
AF XY:
0.00623
AC XY:
4523
AN XY:
725590
show subpopulations
Gnomad4 AFR exome
AF:
0.000867
Gnomad4 AMR exome
AF:
0.00177
Gnomad4 ASJ exome
AF:
0.000268
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000986
Gnomad4 FIN exome
AF:
0.00804
Gnomad4 NFE exome
AF:
0.00755
Gnomad4 OTH exome
AF:
0.00408
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00468
AC:
713
AN:
152338
Hom.:
5
Cov.:
33
AF XY:
0.00450
AC XY:
335
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.00120
Gnomad4 AMR
AF:
0.00366
Gnomad4 ASJ
AF:
0.000864
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000622
Gnomad4 FIN
AF:
0.00923
Gnomad4 NFE
AF:
0.00726
Gnomad4 OTH
AF:
0.00378
Alfa
AF:
0.00519
Hom.:
1
Bravo
AF:
0.00400
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00671
EpiControl
AF:
0.00848

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenOct 01, 2022IGSF9B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.65
Cadd
Benign
2.3
Dann
Benign
0.84

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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

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

Other links and lift over

dbSNP: rs150544201; hg19: chr11-133791166; API