rs11604082

Variant names:

• chr11-126598817-T-C
• rs11604082
• NM_032531.4:c.56-35905A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032531.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIRREL3	NM_032531.4	MANE Select	c.56-35905A>G		intron	N/A	NP_115920.1	Q8IZU9-1
	KIRREL3	NM_001441252.1		c.56-35905A>G		intron	N/A	NP_001428181.1
	KIRREL3	NM_001441253.1		c.56-35905A>G		intron	N/A	NP_001428182.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIRREL3	ENST00000525144.7	TSL:1 MANE Select	c.56-35905A>G		intron	N/A	ENSP00000435466.2	Q8IZU9-1
	KIRREL3	ENST00000529097.6	TSL:1	c.56-35905A>G		intron	N/A	ENSP00000434081.2	E9PRX9
	KIRREL3	ENST00000525704.2	TSL:1	c.56-35905A>G		intron	N/A	ENSP00000435094.2	Q8IZU9-2

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

African (AFR) AF: 0.0368 AC: 1529 AN: 41554

American (AMR) AF: 0.0886 AC: 1355 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 470 AN: 3470

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5178

South Asian (SAS) AF: 0.0361 AC: 174 AN: 4824

European-Finnish (FIN) AF: 0.125 AC: 1324 AN: 10604

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8445 AN: 68018

Other (OTH) AF: 0.0949 AC: 200 AN: 2108

Alfa AF: 0.113 Hom.: 543

Bravo AF: 0.0849

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.37
DANN	Benign	0.63
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11604082; hg19: chr11-126468712;