chr5-179813910-A-C

Position:

• chr5-179813910-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142298.2(SQSTM1):​c.-48+2228A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 152,110 control chromosomes in the GnomAD database, including 45,229 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 0.76 (45229 hom., cov: 32)
• Consequence: SQSTM1 NM_001142298.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SQSTM1	NM_001142298.2	c.-48+2228A>C		intron_variant			NP_001135770.1
SQSTM1	NM_001142299.2	c.-48+2228A>C		intron_variant			NP_001135771.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SQSTM1	ENST00000514093.5	c.-48+2228A>C		intron_variant		5		ENSP00000427308

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115872 AN: 151992 Hom.: 45195 Cov.: 32

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.864

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.782

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

GnomAD4 genome AF: 0.762 AC: 115958 AN: 152110 Hom.: 45229 Cov.: 32 AF XY: 0.766 AC XY: 56968 AN XY: 74362

Gnomad4 AFR AF: 0.580

Gnomad4 AMR AF: 0.805

Gnomad4 ASJ AF: 0.787

Gnomad4 EAS AF: 0.732

Gnomad4 SAS AF: 0.829

Gnomad4 FIN AF: 0.864

Gnomad4 NFE AF: 0.844

Gnomad4 OTH AF: 0.784

Alfa AF: 0.825 Hom.: 78914

Bravo AF: 0.747

Asia WGS AF: 0.777 AC: 2703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.1
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10516140; hg19: chr5-179240910; COSMIC: COSV65364126;