rs72807343

Positions:

• chr5-179811261-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001142298.2(SQSTM1):​c.-156-313C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 151,424 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.016 (39 hom., cov: 26)
• Consequence: SQSTM1 NM_001142298.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0164 (2476/151424) while in subpopulation AFR AF= 0.0217 (895/41244). AF 95% confidence interval is 0.0205. There are 39 homozygotes in gnomad4. There are 1137 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2476 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SQSTM1	NM_001142298.2	c.-156-313C>T		intron_variant			NP_001135770.1
SQSTM1	NM_001142299.2	c.-156-313C>T		intron_variant			NP_001135771.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SQSTM1	ENST00000514093.5	c.-156-313C>T		intron_variant		5		ENSP00000427308.1
SQSTM1	ENST00000506042.5	n.195-313C>T		intron_variant		2
SQSTM1	ENST00000506690.1	n.1105-313C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0164 AC: 2476 AN: 151322 Hom.: 38 Cov.: 26

Gnomad AFR AF: 0.0217

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0146

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.00213

Gnomad SAS AF: 0.0163

Gnomad FIN AF: 0.00391

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.0163

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

GnomAD4 genome AF: 0.0164 AC: 2476 AN: 151424 Hom.: 39 Cov.: 26 AF XY: 0.0154 AC XY: 1137 AN XY: 74002

Gnomad4 AFR AF: 0.0217

Gnomad4 AMR AF: 0.0146

Gnomad4 ASJ AF: 0.0274

Gnomad4 EAS AF: 0.00214

Gnomad4 SAS AF: 0.0163

Gnomad4 FIN AF: 0.00391

Gnomad4 NFE AF: 0.0153

Gnomad4 OTH AF: 0.0162

Alfa AF: 0.0164 Hom.: 3

Bravo AF: 0.0170

Asia WGS AF: 0.0130 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.3
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs72807343; hg19: chr5-179238261;