Variant chr11-133931561-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001277285.4(IGSF9B):c.1260C>A(p.Pro420Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00259 in 1,612,688 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 7 hom. )

Consequence

IGSF9B
NM_001277285.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.112

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]

IGSF9B links:

IGSF9B (HGNC:):

IGSF9B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 11-133931561-G-T is Benign according to our data. Variant chr11-133931561-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 708539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.112 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF9B	NM_001277285.4 linkuse as main transcript	c.1260C>A	p.Pro420Pro	synonymous_variant	10/20	ENST00000533871.8	NP_001264214.1	Q9UPX0-2Q8N7W7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IGSF9B	ENST00000533871.8 linkuse as main transcript	c.1260C>A	p.Pro420Pro	synonymous_variant	10/20	5	NM_001277285.4	ENSP00000436552.2	Q9UPX0-2
IGSF9B	ENST00000321016.12 linkuse as main transcript	c.1260C>A	p.Pro420Pro	synonymous_variant	10/19	5		ENSP00000317980.8	Q9UPX0-1
IGSF9B	ENST00000527648.2 linkuse as main transcript	n.990C>A		non_coding_transcript_exon_variant	7/13	2

Frequencies

GnomAD3 genomes

AF:

0.00172

AC:

261

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000917

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00300

Gnomad OTH

AF:

0.000960

GnomAD3 exomes

AF:

0.00174

AC:

431

AN:

247816

Hom.:

AF XY:

0.00175

AC XY:

236

AN XY:

134740

show subpopulations

Gnomad AFR exome

AF:

0.000522

Gnomad AMR exome

AF:

0.000435

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00190

Gnomad NFE exome

AF:

0.00321

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.00269

AC:

3922

AN:

1460514

Hom.:

Cov.:

AF XY:

0.00257

AC XY:

1865

AN XY:

726552

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.000515

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00200

Gnomad4 NFE exome

AF:

0.00329

Gnomad4 OTH exome

AF:

0.00201

GnomAD4 genome

AF:

0.00172

AC:

261

AN:

152174

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

122

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.00300

Gnomad4 OTH

AF:

0.000950

Alfa

AF:

0.00188

Hom.:

Bravo

AF:

0.00160

EpiCase

AF:

0.00180

EpiControl

AF:

0.00291

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 27, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	IGSF9B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.8

DANN

Benign

0.74

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over