rs140965743

Variant names:

• chr3-52502648-C-T
• rs140965743
• NM_015136.3:c.504C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-52502648-C-T
• chr3-52502648-C-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_015136.3(STAB1):​c.504C>T​(p.His168His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0063 in 1,613,310 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0050 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0064 (70 hom.)
• Consequence: STAB1 NM_015136.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.79
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 3-52502648-C-T is Benign according to our data. Variant chr3-52502648-C-T is described in ClinVar as Benign. ClinVar VariationId is 767910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.79 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00503 (767/152338) while in subpopulation SAS AF = 0.023 (111/4828). AF 95% confidence interval is 0.0195. There are 4 homozygotes in GnomAd4. There are 398 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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.504C>T	p.His168His	synonymous	Exon 6 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.504C>T	p.His168His	synonymous	Exon 6 of 69	ENSP00000312946.6	Q9NY15-1
	STAB1	ENST00000481607.1	TSL:1	n.559C>T		non_coding_transcript_exon	Exon 6 of 21
	STAB1	ENST00000899926.1		c.504C>T	p.His168His	synonymous	Exon 6 of 69	ENSP00000569985.1

Frequencies

GnomAD3 genomes AF: 0.00506 AC: 770 AN: 152220 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00499

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0234

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00525

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00630 AC: 1579 AN: 250594 AF XY: 0.00733

Gnomad AFR exome AF: 0.00463

Gnomad AMR exome AF: 0.00234

Gnomad ASJ exome AF: 0.00159

Gnomad EAS exome AF: 0.000816

Gnomad FIN exome AF: 0.00171

Gnomad NFE exome AF: 0.00503

Gnomad OTH exome AF: 0.00295

GnomAD4 exome AF: 0.00644 AC: 9402 AN: 1460972 Hom.: 70 Cov.: 32 AF XY: 0.00699 AC XY: 5076 AN XY: 726682

African (AFR) AF: 0.00505 AC: 169 AN: 33468

American (AMR) AF: 0.00230 AC: 103 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00161 AC: 42 AN: 26132

East Asian (EAS) AF: 0.000655 AC: 26 AN: 39674

South Asian (SAS) AF: 0.0247 AC: 2133 AN: 86248

European-Finnish (FIN) AF: 0.00162 AC: 86 AN: 53058

Middle Eastern (MID) AF: 0.00555 AC: 32 AN: 5768

European-Non Finnish (NFE) AF: 0.00579 AC: 6437 AN: 1111548

Other (OTH) AF: 0.00620 AC: 374 AN: 60366

GnomAD4 genome AF: 0.00503 AC: 767 AN: 152338 Hom.: 4 Cov.: 33 AF XY: 0.00534 AC XY: 398 AN XY: 74484

African (AFR) AF: 0.00498 AC: 207 AN: 41582

American (AMR) AF: 0.00359 AC: 55 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5188

South Asian (SAS) AF: 0.0230 AC: 111 AN: 4828

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00523 AC: 356 AN: 68026

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00460 Hom.: 2

Bravo AF: 0.00437

Asia WGS AF: 0.00866 AC: 30 AN: 3478

EpiCase AF: 0.00431

EpiControl AF: 0.00563

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.48
DANN	Benign	0.30
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs140965743; hg19: chr3-52536664; COSMIC: COSV58734964; COSMIC: COSV58734964;