rs2242330

Variant names:

• chr4-67581531-A-G
• rs2242330
• NM_012108.4:c.530+60A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-67581531-A-G
• chr4-67581531-A-C
• chr4-67581531-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012108.4(STAP1):​c.530+60A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,537,914 control chromosomes in the GnomAD database, including 38,752 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3171 hom., cov: 33)
  • Exomes 𝑓: 0.22 (35581 hom.)
• Consequence: STAP1 NM_012108.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.308
• Publications: 25 publications found

Genes affected

STAP1 (HGNC:24133): (signal transducing adaptor family member 1) The protein encoded by this gene contains a proline-rich region, a pleckstrin homology (PH) domain, and a region in the carboxy terminal half with similarity to the Src Homology 2 (SH2) domain. This protein is a substrate of tyrosine-protein kinase Tec, and its interaction with tyrosine-protein kinase Tec is phosphorylation-dependent. This protein is thought to participate in a positive feedback loop by upregulating the activity of tyrosine-protein kinase Tec. Variants of this gene have been associated with autosomal-dominant hypercholesterolemia (ADH), which is characterized by elevated low-density lipoprotein cholesterol levels and in increased risk of coronary vascular disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 4-67581531-A-G is Benign according to our data. Variant chr4-67581531-A-G is described in ClinVar as Benign. ClinVar VariationId is 1262529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012108.4. 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
	STAP1	NM_012108.4	MANE Select	c.530+60A>G		intron	N/A	NP_036240.1	Q9ULZ2
	STAP1	NM_001317769.2		c.530+60A>G		intron	N/A	NP_001304698.1	Q9ULZ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAP1	ENST00000265404.7	TSL:1 MANE Select	c.530+60A>G		intron	N/A	ENSP00000265404.2	Q9ULZ2
	STAP1	ENST00000396225.1	TSL:1	c.530+60A>G		intron	N/A	ENSP00000379527.1	Q9ULZ2
	STAP1	ENST00000894638.1		c.530+60A>G		intron	N/A	ENSP00000564697.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30072 AN: 152056 Hom.: 3176 Cov.: 33

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.194

GnomAD4 exome AF: 0.223 AC: 309202 AN: 1385740 Hom.: 35581 AF XY: 0.226 AC XY: 154373 AN XY: 683322

African (AFR) AF: 0.124 AC: 3896 AN: 31324

American (AMR) AF: 0.149 AC: 5447 AN: 36482

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 5346 AN: 22088

East Asian (EAS) AF: 0.183 AC: 7130 AN: 38898

South Asian (SAS) AF: 0.312 AC: 22545 AN: 72290

European-Finnish (FIN) AF: 0.286 AC: 14520 AN: 50816

Middle Eastern (MID) AF: 0.232 AC: 1255 AN: 5418

European-Non Finnish (NFE) AF: 0.221 AC: 236371 AN: 1071200

Other (OTH) AF: 0.222 AC: 12692 AN: 57224

GnomAD4 genome AF: 0.198 AC: 30060 AN: 152174 Hom.: 3171 Cov.: 33 AF XY: 0.202 AC XY: 15049 AN XY: 74396

African (AFR) AF: 0.128 AC: 5327 AN: 41524

American (AMR) AF: 0.171 AC: 2618 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 791 AN: 3468

East Asian (EAS) AF: 0.229 AC: 1184 AN: 5168

South Asian (SAS) AF: 0.303 AC: 1462 AN: 4822

European-Finnish (FIN) AF: 0.287 AC: 3035 AN: 10568

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15089 AN: 68002

Other (OTH) AF: 0.190 AC: 402 AN: 2114

Alfa AF: 0.210 Hom.: 14841

Bravo AF: 0.183

Asia WGS AF: 0.213 AC: 740 AN: 3478

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	-0.64
CADD	Benign	11
DANN	Benign	0.57
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs2242330; hg19: chr4-68447249; COSMIC: COSV55327755;