rs3926407

chr11-126726922-C-T

Variant summary

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

The NM_032531.4(KIRREL3):c.56-164010G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 152,172 control chromosomes in the GnomAD database, including 46,482 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 0.78 (46482 hom., cov: 33)
• Consequence: KIRREL3 NM_032531.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790

Genes affected

KIRREL3 (HGNC:23204): (kirre like nephrin family adhesion molecule 3) The protein encoded by this gene is a member of the nephrin-like protein family. These proteins are expressed in fetal and adult brain, and also in podocytes of kidney glomeruli. The cytoplasmic domains of these proteins interact with the C-terminus of podocin, also expressed in the podocytes, cells involved in ensuring size- and charge-selective ultrafiltration. The protein encoded by this gene is a synaptic cell adhesion molecule with multiple extracellular immunoglobulin-like domains and a cytoplasmic PDZ domain-binding motif. Mutations in this gene are associated with several neurological and cognitive disorders. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIRREL3	NM_032531.4	c.56-164010G>A		intron_variant		ENST00000525144.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIRREL3	ENST00000525144.7	c.56-164010G>A		intron_variant		1	NM_032531.4	P4

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118228 AN: 152054 Hom.: 46457 Cov.: 33

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.942

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.910

Gnomad FIN AF: 0.821

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.779

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

GnomAD4 genome AF: 0.777 AC: 118298 AN: 152172 Hom.: 46482 Cov.: 33 AF XY: 0.783 AC XY: 58240 AN XY: 74382

Gnomad4 AFR AF: 0.666

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.816

Gnomad4 EAS AF: 0.986

Gnomad4 SAS AF: 0.910

Gnomad4 FIN AF: 0.821

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.780

Alfa AF: 0.801 Hom.: 28209

Bravo AF: 0.769

Asia WGS AF: 0.915 AC: 3179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.53
Dann	Benign	0.70

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: rs3926407; hg19: chr11-126596817;