11-133925324-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001277285.4(IGSF9B):c.2034+415A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 152,186 control chromosomes in the GnomAD database, including 50,195 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.81 (50195 hom., cov: 33)
• Consequence: IGSF9B NM_001277285.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.847

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGSF9B	NM_001277285.4	c.2034+415A>G		intron_variant		ENST00000533871.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGSF9B	ENST00000533871.8	c.2034+415A>G		intron_variant		5	NM_001277285.4	P1
IGSF9B	ENST00000321016.12	c.2034+415A>G		intron_variant		5
IGSF9B	ENST00000527648.2	n.1764+415A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.809 AC: 122985 AN: 152068 Hom.: 50165 Cov.: 33

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.831

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.809 AC: 123074 AN: 152186 Hom.: 50195 Cov.: 33 AF XY: 0.807 AC XY: 60057 AN XY: 74406

Gnomad4 AFR AF: 0.711

Gnomad4 AMR AF: 0.796

Gnomad4 ASJ AF: 0.862

Gnomad4 EAS AF: 0.867

Gnomad4 SAS AF: 0.767

Gnomad4 FIN AF: 0.859

Gnomad4 NFE AF: 0.859

Gnomad4 OTH AF: 0.832

Alfa AF: 0.847 Hom.: 49408

Bravo AF: 0.797

Asia WGS AF: 0.818 AC: 2843 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	1.4
Dann	Benign	0.61

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: rs329668; hg19: chr11-133795219;