Variant 11-127000522-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000525144.7(KIRREL3):c.-13G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0467 in 1,600,170 control chromosomes in the GnomAD database, including 5,187 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 0.080 ( 1050 hom., cov: 32)

Exomes 𝑓: 0.043 ( 4137 hom. )

Consequence

KIRREL3
ENST00000525144.7 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.189

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIRREL3	NM_032531.4 linkuse as main transcript	c.-13G>A		5_prime_UTR_variant	1/17	ENST00000525144.7	NP_115920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIRREL3	ENST00000525144.7 linkuse as main transcript	c.-13G>A		5_prime_UTR_variant	1/17	1	NM_032531.4	ENSP00000435466	P4	Q8IZU9-1

Frequencies

GnomAD3 genomes

AF:

0.0798

AC:

12129

AN:

152052

Hom.:

1044

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.0598

Gnomad ASJ

AF:

0.0337

Gnomad EAS

AF:

0.419

Gnomad SAS

AF:

0.0777

Gnomad FIN

AF:

0.0254

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.0280

Gnomad OTH

AF:

0.0751

GnomAD3 exomes

AF:

0.0706

AC:

15804

AN:

223834

Hom.:

1757

AF XY:

0.0672

AC XY:

8122

AN XY:

120782

show subpopulations

Gnomad AFR exome

AF:

0.146

Gnomad AMR exome

AF:

0.0491

Gnomad ASJ exome

AF:

0.0298

Gnomad EAS exome

AF:

0.429

Gnomad SAS exome

AF:

0.0594

Gnomad FIN exome

AF:

0.0272

Gnomad NFE exome

AF:

0.0282

Gnomad OTH exome

AF:

0.0510

GnomAD4 exome

AF:

0.0433

AC:

62651

AN:

1448000

Hom.:

4137

Cov.:

AF XY:

0.0434

AC XY:

31223

AN XY:

718700

show subpopulations

Gnomad4 AFR exome

AF:

0.150

Gnomad4 AMR exome

AF:

0.0515

Gnomad4 ASJ exome

AF:

0.0298

Gnomad4 EAS exome

AF:

0.364

Gnomad4 SAS exome

AF:

0.0620

Gnomad4 FIN exome

AF:

0.0299

Gnomad4 NFE exome

AF:

0.0270

Gnomad4 OTH exome

AF:

0.0655

GnomAD4 genome

AF:

0.0799

AC:

12156

AN:

152170

Hom.:

1050

Cov.:

AF XY:

0.0812

AC XY:

6039

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.149

Gnomad4 AMR

AF:

0.0597

Gnomad4 ASJ

AF:

0.0337

Gnomad4 EAS

AF:

0.419

Gnomad4 SAS

AF:

0.0774

Gnomad4 FIN

AF:

0.0254

Gnomad4 NFE

AF:

0.0280

Gnomad4 OTH

AF:

0.0810

Alfa

AF:

0.0391

Hom.:

155

Bravo

AF:

0.0873

Asia WGS

AF:

0.226

AC:

782

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.90

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over