11-133931561-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001277285.4(IGSF9B):c.1260C>A(p.Pro420=) 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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.112

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 -13 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGSF9B	NM_001277285.4	c.1260C>A	p.Pro420=	synonymous_variant	10/20	ENST00000533871.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGSF9B	ENST00000533871.8	c.1260C>A	p.Pro420=	synonymous_variant	10/20	5	NM_001277285.4	P1
IGSF9B	ENST00000321016.12	c.1260C>A	p.Pro420=	synonymous_variant	10/19	5
IGSF9B	ENST00000527648.2	n.990C>A		non_coding_transcript_exon_variant	7/13	2

Frequencies

GnomAD3 genomes AF: 0.00172 AC: 261 AN: 152056 Hom.: 0 Cov.: 32

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.: 1 AF XY: 0.00175 AC XY: 236 AN XY: 134740

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.: 7 Cov.: 33 AF XY: 0.00257 AC XY: 1865 AN XY: 726552

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.: 0 Cov.: 32 AF XY: 0.00164 AC XY: 122 AN XY: 74396

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.: 1

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

Submissions by phenotype

not provided Benign:2

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

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

Other links and lift over

dbSNP: rs182620767; hg19: chr11-133801456;