5-179820747-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001142298.2(SQSTM1):c.-47-2211G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0166 in 503,212 control chromosomes in the GnomAD database, including 576 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.044 (476 hom., cov: 33)
  • Exomes 𝑓: 0.0049 (100 hom.)
• Consequence: SQSTM1 NM_001142298.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0170

Genes affected

SQSTM1 (HGNC:11280): (sequestosome 1) This gene encodes a multifunctional protein that binds ubiquitin and regulates activation of the nuclear factor kappa-B (NF-kB) signaling pathway. The protein functions as a scaffolding/adaptor protein in concert with TNF receptor-associated factor 6 to mediate activation of NF-kB in response to upstream signals. Alternatively spliced transcript variants encoding either the same or different isoforms have been identified for this gene. Mutations in this gene result in sporadic and familial Paget disease of bone. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 5-179820747-G-A is Benign according to our data. Variant chr5-179820747-G-A is described in ClinVar as [Benign]. Clinvar id is 1261854.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SQSTM1	NM_001142298.2	c.-47-2211G>A		intron_variant
SQSTM1	NM_001142299.2	c.-47-2211G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SQSTM1	ENST00000422245.5	c.-48+1710G>A		intron_variant		4
SQSTM1	ENST00000514093.5	c.-47-2211G>A		intron_variant		5
SQSTM1	ENST00000464493.5	n.100+41G>A		intron_variant, non_coding_transcript_variant		4
SQSTM1	ENST00000481335.5	n.355+360G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0437 AC: 6651 AN: 152134 Hom.: 477 Cov.: 33

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000662

Gnomad OTH AF: 0.0358

GnomAD4 exome AF: 0.00489 AC: 1715 AN: 350960 Hom.: 100 Cov.: 5 AF XY: 0.00396 AC XY: 726 AN XY: 183320

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.0162

Gnomad4 ASJ exome AF: 0.00232

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000410

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000453

Gnomad4 OTH exome AF: 0.0144

GnomAD4 genome AF: 0.0438 AC: 6662 AN: 152252 Hom.: 476 Cov.: 33 AF XY: 0.0412 AC XY: 3070 AN XY: 74450

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.0225

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000662

Gnomad4 OTH AF: 0.0354

Alfa AF: 0.00215 Hom.: 4

Bravo AF: 0.0519

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	4.2
Dann	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2516294; hg19: chr5-179247747;