rs11604082

Positions:

• chr11-126598817-T-C

Variant summary

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

The NM_032531.4(KIRREL3):​c.56-35905A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0892 in 152,258 control chromosomes in the GnomAD database, including 714 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 0.089 (714 hom., cov: 33)
• Consequence: KIRREL3 NM_032531.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.827

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIRREL3	NM_032531.4	c.56-35905A>G		intron_variant		ENST00000525144.7	NP_115920.1
KIRREL3-AS1	NR_174952.1	n.419-11844T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIRREL3	ENST00000525144.7	c.56-35905A>G		intron_variant		1	NM_032531.4	ENSP00000435466	P4
KIRREL3-AS1	ENST00000548204.1	n.299-11844T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0893 AC: 13588 AN: 152140 Hom.: 715 Cov.: 33

Gnomad AFR AF: 0.0369

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0887

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0367

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.0959

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

GnomAD4 genome AF: 0.0892 AC: 13579 AN: 152258 Hom.: 714 Cov.: 33 AF XY: 0.0873 AC XY: 6500 AN XY: 74444

Gnomad4 AFR AF: 0.0368

Gnomad4 AMR AF: 0.0886

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0361

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.0949

Alfa AF: 0.113 Hom.: 483

Bravo AF: 0.0849

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.37
DANN	Benign	0.63

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: rs11604082; hg19: chr11-126468712;