rs4935969

Variant names:

• chr11-126426694-C-T
• rs4935969
• NM_032531.4:c.1807-970G>A

Variant summary

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

The NM_032531.4(KIRREL3):​c.1807-970G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,004 control chromosomes in the GnomAD database, including 12,183 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 0.38 (12183 hom., cov: 32)
• Consequence: KIRREL3 NM_032531.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.85
• Publications: 10 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]

ST3GAL4 (HGNC:10864): (ST3 beta-galactoside alpha-2,3-sialyltransferase 4) This gene encodes a member of the glycosyltransferase 29 family, a group of enzymes involved in protein glycosylation. The encoded protein is targeted to Golgi membranes but may be proteolytically processed and secreted. The gene product may also be involved in the increased expression of sialyl Lewis X antigen seen in inflammatory responses. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.853 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.1807-970G>A		intron	N/A	NP_115920.1	Q8IZU9-1
	KIRREL3	NM_001441252.1		c.1915-970G>A		intron	N/A	NP_001428181.1
	KIRREL3	NM_001441253.1		c.1882-970G>A		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.1807-970G>A		intron	N/A	ENSP00000435466.2	Q8IZU9-1
	KIRREL3	ENST00000529097.6	TSL:1	c.1771-970G>A		intron	N/A	ENSP00000434081.2	E9PRX9
	ST3GAL4	ENST00000524834.5	TSL:2	n.630-13492C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57151 AN: 151886 Hom.: 12172 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.874

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.376 AC: 57189 AN: 152004 Hom.: 12183 Cov.: 32 AF XY: 0.388 AC XY: 28854 AN XY: 74286

African (AFR) AF: 0.220 AC: 9132 AN: 41464

American (AMR) AF: 0.449 AC: 6849 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1748 AN: 3464

East Asian (EAS) AF: 0.874 AC: 4519 AN: 5168

South Asian (SAS) AF: 0.520 AC: 2498 AN: 4808

European-Finnish (FIN) AF: 0.458 AC: 4831 AN: 10550

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.386 AC: 26237 AN: 67974

Other (OTH) AF: 0.411 AC: 867 AN: 2110

Alfa AF: 0.397 Hom.: 55738

Bravo AF: 0.370

Asia WGS AF: 0.628 AC: 2183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.013
DANN	Benign	0.62
PhyloP100		-3.9
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4935969;

hg19: chr11-126296589;

COSMIC: COSV69384703;

COSMIC: COSV69384703;