rs13138607

Positions:

• chr4-67755832-G-A
• chr4-67755832-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000500538.7(UBA6-DT):​n.1987+577G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,746 control chromosomes in the GnomAD database, including 16,633 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.45 (16633 hom., cov: 32)
• Consequence: UBA6-DT ENST00000500538.7 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.365

Genes affected

UBA6-DT (HGNC:49083): (UBA6 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 4-67755832-G-A is Benign according to our data. Variant chr4-67755832-G-A is described in ClinVar as [Benign]. Clinvar id is 349482.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBA6-DT	ENST00000500538.7	n.1987+577G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 67870 AN: 151632 Hom.: 16617 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.448 AC: 67909 AN: 151746 Hom.: 16633 Cov.: 32 AF XY: 0.454 AC XY: 33654 AN XY: 74136

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.560

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.455

Alfa AF: 0.486 Hom.: 8488

Bravo AF: 0.433

Asia WGS AF: 0.590 AC: 2051 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hypogonadotropic hypogonadism 7 with or without anosmia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.9
DANN	Benign	0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13138607; hg19: chr4-68621550;