rs492125

Positions:

• chr11-126574827-G-C

Variant summary

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

The NM_032531.4(KIRREL3):​c.56-11915C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,110 control chromosomes in the GnomAD database, including 10,792 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 0.36 (10792 hom., cov: 33)
• Consequence: KIRREL3 NM_032531.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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]

KIRREL3-AS1 (HGNC:42655): (KIRREL3 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIRREL3	NM_032531.4	c.56-11915C>G		intron_variant		ENST00000525144.7
KIRREL3-AS1	NR_174952.1	n.418+30583G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIRREL3	ENST00000525144.7	c.56-11915C>G		intron_variant		1	NM_032531.4	P4
KIRREL3-AS1	ENST00000548204.1	n.298+30583G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54291 AN: 151992 Hom.: 10783 Cov.: 33

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.357 AC: 54312 AN: 152110 Hom.: 10792 Cov.: 33 AF XY: 0.355 AC XY: 26420 AN XY: 74358

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.449

Gnomad4 OTH AF: 0.397

Alfa AF: 0.396 Hom.: 1559

Bravo AF: 0.349

Asia WGS AF: 0.443 AC: 1541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.13
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: rs492125; hg19: chr11-126444722;