11-126440261-G-A

Variant names:

• chr11-126440261-G-A
• rs3740918
• NM_032531.4:c.1353+188C>T

Variant summary

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

The NM_032531.4(KIRREL3):​c.1353+188C>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 709,014 control chromosomes in the GnomAD database, including 27,661 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 0.31 (8289 hom., cov: 33)
  • Exomes 𝑓: 0.25 (19372 hom.)
• Consequence: KIRREL3 NM_032531.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIRREL3	NM_032531.4	MANE Select	c.1353+188C>T		intron	N/A	NP_115920.1
	KIRREL3	NM_001441252.1		c.1461+188C>T		intron	N/A	NP_001428181.1
	KIRREL3	NM_001441253.1		c.1353+188C>T		intron	N/A	NP_001428182.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIRREL3	ENST00000525144.7	TSL:1 MANE Select	c.1353+188C>T		intron	N/A	ENSP00000435466.2
	KIRREL3	ENST00000529097.6	TSL:1	c.1353+188C>T		intron	N/A	ENSP00000434081.2
	KIRREL3	ENST00000525704.2	TSL:1	c.1353+188C>T		intron	N/A	ENSP00000435094.2

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47665 AN: 151992 Hom.: 8269 Cov.: 33

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.335

GnomAD2 exomes AF: 0.244 AC: 33582 AN: 137726 AF XY: 0.240

Gnomad AFR exome AF: 0.456

Gnomad AMR exome AF: 0.196

Gnomad ASJ exome AF: 0.407

Gnomad EAS exome AF: 0.148

Gnomad FIN exome AF: 0.229

Gnomad NFE exome AF: 0.270

Gnomad OTH exome AF: 0.288

GnomAD4 exome AF: 0.254 AC: 141435 AN: 556904 Hom.: 19372 Cov.: 5 AF XY: 0.249 AC XY: 74931 AN XY: 301166

African (AFR) AF: 0.463 AC: 7355 AN: 15870

American (AMR) AF: 0.205 AC: 7099 AN: 34608

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 7980 AN: 19998

East Asian (EAS) AF: 0.141 AC: 4506 AN: 31964

South Asian (SAS) AF: 0.155 AC: 9599 AN: 62094

European-Finnish (FIN) AF: 0.231 AC: 7735 AN: 33418

Middle Eastern (MID) AF: 0.319 AC: 1300 AN: 4076

European-Non Finnish (NFE) AF: 0.269 AC: 87116 AN: 324172

Other (OTH) AF: 0.285 AC: 8745 AN: 30704

GnomAD4 genome AF: 0.314 AC: 47727 AN: 152110 Hom.: 8289 Cov.: 33 AF XY: 0.306 AC XY: 22724 AN XY: 74382

African (AFR) AF: 0.459 AC: 19021 AN: 41466

American (AMR) AF: 0.258 AC: 3950 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1433 AN: 3470

East Asian (EAS) AF: 0.144 AC: 747 AN: 5178

South Asian (SAS) AF: 0.139 AC: 669 AN: 4830

European-Finnish (FIN) AF: 0.224 AC: 2373 AN: 10586

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18302 AN: 67972

Other (OTH) AF: 0.333 AC: 703 AN: 2114

Alfa AF: 0.286 Hom.: 20264

Bravo AF: 0.327

Asia WGS AF: 0.145 AC: 505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.79
PhyloP100		-0.041
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: rs3740918; hg19: chr11-126310156; COSMIC: COSV69383732;