11-133920493-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001277285.4(IGSF9B):c.3232C>A(p.Arg1078=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000559 in 1,582,696 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00064 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00055 (4 hom.)
• Consequence: IGSF9B NM_001277285.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.28

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 11-133920493-G-T is Benign according to our data. Variant chr11-133920493-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642550.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGSF9B	NM_001277285.4	c.3232C>A	p.Arg1078=	synonymous_variant	18/20	ENST00000533871.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGSF9B	ENST00000533871.8	c.3232C>A	p.Arg1078=	synonymous_variant	18/20	5	NM_001277285.4	P1
IGSF9B	ENST00000321016.12	c.3232C>A	p.Arg1078=	synonymous_variant	18/19	5

Frequencies

GnomAD3 genomes AF: 0.000638 AC: 97 AN: 152050 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00121

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000584 AC: 129 AN: 220940 Hom.: 2 AF XY: 0.000644 AC XY: 77 AN XY: 119514

Gnomad AFR exome AF: 0.0000692

Gnomad AMR exome AF: 0.0000616

Gnomad ASJ exome AF: 0.000807

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000421

Gnomad NFE exome AF: 0.00108

Gnomad OTH exome AF: 0.000938

GnomAD4 exome AF: 0.000551 AC: 788 AN: 1430528 Hom.: 4 Cov.: 34 AF XY: 0.000630 AC XY: 446 AN XY: 708018

Gnomad4 AFR exome AF: 0.0000911

Gnomad4 AMR exome AF: 0.0000937

Gnomad4 ASJ exome AF: 0.000711

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000740

Gnomad4 NFE exome AF: 0.000646

Gnomad4 OTH exome AF: 0.000305

GnomAD4 genome AF: 0.000637 AC: 97 AN: 152168 Hom.: 0 Cov.: 33 AF XY: 0.000565 AC XY: 42 AN XY: 74382

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00121

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000956 Hom.: 0

Bravo AF: 0.000495

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

IGSF9B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	11
Dann	Benign	0.55

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

Other links and lift over

dbSNP: rs187022741; hg19: chr11-133790388; COSMIC: COSV58068583; COSMIC: COSV58068583;