11-126922911-T-C

Position:

• chr11-126922911-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.55+77544A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 152,024 control chromosomes in the GnomAD database, including 39,780 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 0.72 (39780 hom., cov: 32)
• Consequence: KIRREL3 NM_032531.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.08).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIRREL3	NM_032531.4	c.55+77544A>G		intron_variant		ENST00000525144.7	NP_115920.1
LOC105369559	XR_007062939.1	n.190+17538A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIRREL3	ENST00000525144.7	c.55+77544A>G		intron_variant		1	NM_032531.4	ENSP00000435466	P4
	ENST00000530572.1	n.212-2369A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108774 AN: 151906 Hom.: 39761 Cov.: 32

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.738

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

GnomAD4 genome AF: 0.716 AC: 108839 AN: 152024 Hom.: 39780 Cov.: 32 AF XY: 0.710 AC XY: 52741 AN XY: 74322

Gnomad4 AFR AF: 0.829

Gnomad4 AMR AF: 0.687

Gnomad4 ASJ AF: 0.784

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.648

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.731

Alfa AF: 0.715 Hom.: 10222

Bravo AF: 0.726

Asia WGS AF: 0.509 AC: 1774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.19
DANN	Benign	0.062

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: rs1793667; hg19: chr11-126792807;