rs631562

chr11-126982542-A-Cchr11-126982542-A-G

Variant summary

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

The NM_032531.4(KIRREL3):c.55+17913T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 152,056 control chromosomes in the GnomAD database, including 22,033 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 0.53 (22033 hom., cov: 33)
• Consequence: KIRREL3 NM_032531.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.995

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIRREL3	NM_032531.4	c.55+17913T>G		intron_variant		ENST00000525144.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIRREL3	ENST00000525144.7	c.55+17913T>G		intron_variant		1	NM_032531.4	P4

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80095 AN: 151938 Hom.: 22007 Cov.: 33

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.527 AC: 80168 AN: 152056 Hom.: 22033 Cov.: 33 AF XY: 0.531 AC XY: 39485 AN XY: 74334

Gnomad4 AFR AF: 0.648

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.834

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.497

Alfa AF: 0.466 Hom.: 35157

Bravo AF: 0.535

Asia WGS AF: 0.627 AC: 2179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.83
Dann	Benign	0.37

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: rs631562; hg19: chr11-126852438;