Variant 5-179820798-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001142298.2(SQSTM1):c.-47-2160G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 822,616 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 17 hom., cov: 34)

Exomes 𝑓: 0.0016 ( 9 hom. )

Consequence

SQSTM1
NM_001142298.2 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0170

Variant links:

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]

SQSTM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 5-179820798-G-C is Benign according to our data. Variant chr5-179820798-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1214418.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0088 (1340/152276) while in subpopulation AFR AF= 0.0296 (1230/41568). AF 95% confidence interval is 0.0282. There are 17 homozygotes in gnomad4. There are 613 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1340 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SQSTM1	NM_001142298.2 linkuse as main transcript	c.-47-2160G>C		intron_variant			NP_001135770.1
SQSTM1	NM_001142299.2 linkuse as main transcript	c.-47-2160G>C		intron_variant			NP_001135771.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein
SQSTM1	ENST00000422245.5 linkuse as main transcript	c.-48+1761G>C	intron_variant	4	ENSP00000394534
SQSTM1	ENST00000514093.5 linkuse as main transcript	c.-47-2160G>C	intron_variant	5	ENSP00000427308
SQSTM1	ENST00000464493.5 linkuse as main transcript	n.100+92G>C	intron_variant, non_coding_transcript_variant	4
SQSTM1	ENST00000481335.5 linkuse as main transcript	n.355+411G>C	intron_variant, non_coding_transcript_variant	4

Frequencies

GnomAD3 genomes

AF:

0.00879

AC:

1337

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0296

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000750

Gnomad OTH

AF:

0.00862

GnomAD4 exome

AF:

0.00161

AC:

1082

AN:

670340

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

517

AN XY:

336476

show subpopulations

Gnomad4 AFR exome

AF:

0.0307

Gnomad4 AMR exome

AF:

0.00324

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000505

Gnomad4 FIN exome

AF:

0.0000687

Gnomad4 NFE exome

AF:

0.00105

Gnomad4 OTH exome

AF:

0.00337

GnomAD4 genome

AF:

0.00880

AC:

1340

AN:

152276

Hom.:

Cov.:

AF XY:

0.00823

AC XY:

613

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0296

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000735

Gnomad4 OTH

AF:

0.00853

Alfa

AF:

0.00825

Hom.:

Bravo

AF:

0.0101

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.0

DANN

Benign

0.52

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over