rs329640

Positions:

• chr11-133951236-A-G

Variant summary

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

The NM_001277285.4(IGSF9B):​c.65-4978T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 152,062 control chromosomes in the GnomAD database, including 19,850 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 0.50 (19850 hom., cov: 33)
• Consequence: IGSF9B NM_001277285.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF9B	NM_001277285.4	c.65-4978T>C		intron_variant		ENST00000533871.8	NP_001264214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF9B	ENST00000533871.8	c.65-4978T>C		intron_variant		5	NM_001277285.4	ENSP00000436552	P1
IGSF9B	ENST00000321016.12	c.65-4978T>C		intron_variant		5		ENSP00000317980
IGSF9B	ENST00000526663.1	c.205+697T>C		intron_variant		4		ENSP00000435989

Frequencies

GnomAD3 genomes AF: 0.500 AC: 76009 AN: 151946 Hom.: 19805 Cov.: 33

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.501 AC: 76112 AN: 152062 Hom.: 19850 Cov.: 33 AF XY: 0.497 AC XY: 36956 AN XY: 74360

Gnomad4 AFR AF: 0.639

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.503

Alfa AF: 0.464 Hom.: 22134

Bravo AF: 0.502

Asia WGS AF: 0.457 AC: 1591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.2
DANN	Benign	0.44

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: rs329640; hg19: chr11-133821131;