2-224470508-TA-T

Position:

• chr2-224470508-TA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000264414.9(CUL3):​c.*3736del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 231,280 control chromosomes in the GnomAD database, including 4,170 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2933 hom., cov: 29)
  • Exomes 𝑓: 0.16 (1237 hom.)
• Consequence: CUL3 ENST00000264414.9 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00900

Genes affected

CUL3 (HGNC:2553): (cullin 3) This gene encodes a member of the cullin protein family. The encoded protein plays a critical role in the polyubiquitination and subsequent degradation of specific protein substrates as the core component and scaffold protein of an E3 ubiquitin ligase complex. Complexes including the encoded protein may also play a role in late endosome maturation. Mutations in this gene are a cause of type 2E pseudohypoaldosteronism. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-224470508-TA-T is Benign according to our data. Variant chr2-224470508-TA-T is described in ClinVar as [Benign]. Clinvar id is 334574.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUL3	NM_003590.5	c.*3736del		3_prime_UTR_variant	16/16	ENST00000264414.9	NP_003581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUL3	ENST00000264414.9	c.*3736del		3_prime_UTR_variant	16/16	1	NM_003590.5	ENSP00000264414	P1
	ENST00000620050.1	n.242-3471del		intron_variant, non_coding_transcript_variant		5
CUL3	ENST00000344951.8	c.*3736del		3_prime_UTR_variant	15/15	2		ENSP00000343601
	ENST00000622296.1	n.54-2417del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28006 AN: 152030 Hom.: 2922 Cov.: 29

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.163 AC: 12925 AN: 79132 Hom.: 1237 Cov.: 0 AF XY: 0.163 AC XY: 5942 AN XY: 36392

Gnomad4 AFR exome AF: 0.234

Gnomad4 AMR exome AF: 0.211

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.303

Gnomad4 SAS exome AF: 0.259

Gnomad4 FIN exome AF: 0.0517

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.154

GnomAD4 genome AF: 0.184 AC: 28051 AN: 152148 Hom.: 2933 Cov.: 29 AF XY: 0.188 AC XY: 13962 AN XY: 74358

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.178

Alfa AF: 0.157 Hom.: 250

Bravo AF: 0.191

Asia WGS AF: 0.276 AC: 959 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal dominant pseudohypoaldosteronism type 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs5839066; hg19: chr2-225335225;