Variant chr5-179820766-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001142298.2(SQSTM1):c.-47-2192T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00269 in 552,402 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0078 ( 16 hom., cov: 34)

Exomes 𝑓: 0.00077 ( 7 hom. )

Consequence

SQSTM1
NM_001142298.2 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0790

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 5-179820766-T-C is Benign according to our data. Variant chr5-179820766-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1217548.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0078 (1180/151192) while in subpopulation AFR AF= 0.027 (1111/41110). AF 95% confidence interval is 0.0257. There are 16 homozygotes in gnomad4. There are 579 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1180 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SQSTM1	NM_001142298.2 linkuse as main transcript	c.-47-2192T>C		intron_variant
SQSTM1	NM_001142299.2 linkuse as main transcript	c.-47-2192T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL
SQSTM1	ENST00000422245.5 linkuse as main transcript	c.-48+1729T>C	intron_variant	4
SQSTM1	ENST00000514093.5 linkuse as main transcript	c.-47-2192T>C	intron_variant	5
SQSTM1	ENST00000464493.5 linkuse as main transcript	n.100+60T>C	intron_variant, non_coding_transcript_variant	4
SQSTM1	ENST00000481335.5 linkuse as main transcript	n.355+379T>C	intron_variant, non_coding_transcript_variant	4

Frequencies

GnomAD3 genomes

AF:

0.00779

AC:

1177

AN:

151076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00341

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000443

Gnomad OTH

AF:

0.00624

GnomAD4 exome

AF:

0.000768

AC:

308

AN:

401210

Hom.:

Cov.:

AF XY:

0.000588

AC XY:

123

AN XY:

209110

show subpopulations

Gnomad4 AFR exome

AF:

0.0270

Gnomad4 AMR exome

AF:

0.00263

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000926

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000340

Gnomad4 OTH exome

AF:

0.00211

GnomAD4 genome

AF:

0.00780

AC:

1180

AN:

151192

Hom.:

Cov.:

AF XY:

0.00783

AC XY:

579

AN XY:

73906

show subpopulations

Gnomad4 AFR

AF:

0.0270

Gnomad4 AMR

AF:

0.00341

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000443

Gnomad4 OTH

AF:

0.00617

Alfa

AF:

0.00610

Hom.:

Bravo

AF:

0.00897

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 17, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

4.5

DANN

Benign

0.64

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