3-52521941-T-C

Variant names:

• chr3-52521941-T-C
• rs9853056
• NM_015136.3:c.6261T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015136.3(STAB1):​c.6261T>C​(p.Arg2087Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 1,607,774 control chromosomes in the GnomAD database, including 254,042 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. Synonymous variant affecting the same amino acid position (i.e. R2087R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.60 (27979 hom., cov: 34)
  • Exomes 𝑓: 0.55 (226063 hom.)
• Consequence: STAB1 NM_015136.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.58
• Publications: 32 publications found

Genes affected

STAB1 (HGNC:18628): (stabilin 1) This gene encodes a large, transmembrane receptor protein which may function in angiogenesis, lymphocyte homing, cell adhesion, or receptor scavenging. The protein contains 7 fasciclin, 16 epidermal growth factor (EGF)-like, and 2 laminin-type EGF-like domains as well as a C-type lectin-like hyaluronan-binding Link module. The protein is primarily expressed on sinusoidal endothelial cells of liver, spleen, and lymph node. The receptor has been shown to endocytose ligands such as low density lipoprotein, Gram-positive and Gram-negative bacteria, and advanced glycosylation end products. Supporting its possible role as a scavenger receptor, the protein rapidly cycles between the plasma membrane and early endosomes. [provided by RefSeq, Jul 2008]

STAB1 Gene-Disease associations (from GenCC):

• isolated hyperferritinemia

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-2.58 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015136.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAB1	NM_015136.3	MANE Select	c.6261T>C	p.Arg2087Arg	synonymous	Exon 58 of 69	NP_055951.2	Q9NY15-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAB1	ENST00000321725.10	TSL:1 MANE Select	c.6261T>C	p.Arg2087Arg	synonymous	Exon 58 of 69	ENSP00000312946.6	Q9NY15-1
	STAB1	ENST00000462681.1	TSL:1	n.374T>C		non_coding_transcript_exon	Exon 1 of 4
	STAB1	ENST00000899926.1		c.6261T>C	p.Arg2087Arg	synonymous	Exon 58 of 69	ENSP00000569985.1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91159 AN: 151986 Hom.: 27944 Cov.: 34

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.586

GnomAD2 exomes AF: 0.552 AC: 136175 AN: 246672 AF XY: 0.538

Gnomad AFR exome AF: 0.712

Gnomad AMR exome AF: 0.657

Gnomad ASJ exome AF: 0.549

Gnomad EAS exome AF: 0.452

Gnomad FIN exome AF: 0.558

Gnomad NFE exome AF: 0.567

Gnomad OTH exome AF: 0.545

GnomAD4 exome AF: 0.554 AC: 805857 AN: 1455670 Hom.: 226063 Cov.: 63 AF XY: 0.547 AC XY: 395437 AN XY: 723240

African (AFR) AF: 0.720 AC: 24055 AN: 33410

American (AMR) AF: 0.652 AC: 29017 AN: 44474

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 14397 AN: 25828

East Asian (EAS) AF: 0.524 AC: 20755 AN: 39576

South Asian (SAS) AF: 0.354 AC: 30360 AN: 85668

European-Finnish (FIN) AF: 0.554 AC: 29231 AN: 52788

Middle Eastern (MID) AF: 0.531 AC: 3056 AN: 5754

European-Non Finnish (NFE) AF: 0.562 AC: 622251 AN: 1108104

Other (OTH) AF: 0.545 AC: 32735 AN: 60068

GnomAD4 genome AF: 0.600 AC: 91247 AN: 152104 Hom.: 27979 Cov.: 34 AF XY: 0.595 AC XY: 44251 AN XY: 74364

African (AFR) AF: 0.706 AC: 29310 AN: 41496

American (AMR) AF: 0.644 AC: 9850 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1921 AN: 3470

East Asian (EAS) AF: 0.467 AC: 2414 AN: 5164

South Asian (SAS) AF: 0.346 AC: 1667 AN: 4822

European-Finnish (FIN) AF: 0.544 AC: 5763 AN: 10588

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38376 AN: 67954

Other (OTH) AF: 0.591 AC: 1245 AN: 2108

Alfa AF: 0.576 Hom.: 34182

Bravo AF: 0.615

Asia WGS AF: 0.463 AC: 1613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.50
DANN	Benign	0.36
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs9853056; hg19: chr3-52555957; COSMIC: COSV58734418; COSMIC: COSV58734418;