rs6590224

Variant names:

• chr11-126690545-G-A
• rs6590224
• NM_032531.4:c.56-127633C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-126690545-G-A
• chr11-126690545-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032531.4(KIRREL3):​c.56-127633C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 151,930 control chromosomes in the GnomAD database, including 6,148 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 0.27 (6148 hom., cov: 31)
• Consequence: KIRREL3 NM_032531.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403
• Publications: 1 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 Gene-Disease associations (from GenCC):

• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• intellectual disability, autosomal dominant 4

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• complex neurodevelopmental disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000295928 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.405 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.56-127633C>T		intron	N/A	NP_115920.1	Q8IZU9-1
	KIRREL3	NM_001441252.1		c.56-127633C>T		intron	N/A	NP_001428181.1
	KIRREL3	NM_001441253.1		c.56-127633C>T		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.56-127633C>T		intron	N/A	ENSP00000435466.2	Q8IZU9-1
	KIRREL3	ENST00000529097.6	TSL:1	c.56-127633C>T		intron	N/A	ENSP00000434081.2	E9PRX9
	KIRREL3	ENST00000525704.2	TSL:1	c.56-127633C>T		intron	N/A	ENSP00000435094.2	Q8IZU9-2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40542 AN: 151812 Hom.: 6144 Cov.: 31

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.267 AC: 40573 AN: 151930 Hom.: 6148 Cov.: 31 AF XY: 0.262 AC XY: 19464 AN XY: 74272

African (AFR) AF: 0.410 AC: 16954 AN: 41352

American (AMR) AF: 0.214 AC: 3281 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 423 AN: 3466

East Asian (EAS) AF: 0.158 AC: 813 AN: 5160

South Asian (SAS) AF: 0.111 AC: 534 AN: 4824

European-Finnish (FIN) AF: 0.230 AC: 2426 AN: 10560

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15263 AN: 67952

Other (OTH) AF: 0.227 AC: 479 AN: 2112

Alfa AF: 0.295 Hom.: 2648

Bravo AF: 0.278

Asia WGS AF: 0.150 AC: 524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.31
DANN	Benign	0.45
PhyloP100		-0.40
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: rs6590224; hg19: chr11-126560440;