chr3-52502994-C-T

Variant names:

• chr3-52502994-C-T
• rs138643169
• NM_015136.3:c.584-5C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_015136.3(STAB1):​c.584-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00626 in 1,563,412 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0066 (12 hom., cov: 33)
  • Exomes 𝑓: 0.0062 (86 hom.)
• Consequence: STAB1 NM_015136.3 splice_region, intron
• Scores: Splicing: ADA: 0.0001247
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.19
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 3-52502994-C-T is Benign according to our data. Variant chr3-52502994-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2653890.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 12 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.584-5C>T		splice_region intron	N/A	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.584-5C>T		splice_region intron	N/A	ENSP00000312946.6	Q9NY15-1
	STAB1	ENST00000481607.1	TSL:1	n.639-5C>T		splice_region intron	N/A
	STAB1	ENST00000899926.1		c.584-5C>T		splice_region intron	N/A	ENSP00000569985.1

Frequencies

GnomAD3 genomes AF: 0.00664 AC: 1011 AN: 152228 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.000989

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.0505

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00561

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00732 AC: 1387 AN: 189582 AF XY: 0.00758

Gnomad AFR exome AF: 0.000835

Gnomad AMR exome AF: 0.00214

Gnomad ASJ exome AF: 0.000513

Gnomad EAS exome AF: 0.000133

Gnomad FIN exome AF: 0.0486

Gnomad NFE exome AF: 0.00488

Gnomad OTH exome AF: 0.00720

GnomAD4 exome AF: 0.00622 AC: 8775 AN: 1411066 Hom.: 86 Cov.: 33 AF XY: 0.00620 AC XY: 4317 AN XY: 696780

African (AFR) AF: 0.000981 AC: 32 AN: 32628

American (AMR) AF: 0.00205 AC: 80 AN: 38988

Ashkenazi Jewish (ASJ) AF: 0.000909 AC: 22 AN: 24214

East Asian (EAS) AF: 0.0000528 AC: 2 AN: 37902

South Asian (SAS) AF: 0.00503 AC: 396 AN: 78706

European-Finnish (FIN) AF: 0.0436 AC: 2115 AN: 48518

Middle Eastern (MID) AF: 0.00778 AC: 35 AN: 4500

European-Non Finnish (NFE) AF: 0.00529 AC: 5752 AN: 1087194

Other (OTH) AF: 0.00584 AC: 341 AN: 58416

GnomAD4 genome AF: 0.00664 AC: 1012 AN: 152346 Hom.: 12 Cov.: 33 AF XY: 0.00840 AC XY: 626 AN XY: 74500

African (AFR) AF: 0.000986 AC: 41 AN: 41584

American (AMR) AF: 0.00157 AC: 24 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4822

European-Finnish (FIN) AF: 0.0505 AC: 536 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00562 AC: 382 AN: 68030

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00424 Hom.: 0

Bravo AF: 0.00312

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.1
DANN	Benign	0.52
PhyloP100		-1.2
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00012
dbscSNV1_RF	Benign	0.0
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

Other links and lift over

dbSNP: rs138643169; hg19: chr3-52537010;