dbSNP rs4968596: STRADA:c.36+15A>G (chr17-63728319-T-C) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_001003787.4(STRADA):c.36+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,612,884 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 57 hom. )

Consequence

STRADA
NM_001003787.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.167

Publications

1 publications found

Variant links:

Genes affected

STRADA (HGNC:30172): (STE20 related adaptor alpha) The protein encoded by this gene contains a STE20-like kinase domain, but lacks several residues that are critical for catalytic activity, so it is termed a 'pseudokinase'. The protein forms a heterotrimeric complex with serine/threonine kinase 11 (STK11, also known as LKB1) and the scaffolding protein calcium binding protein 39 (CAB39, also known as MO25). The protein activates STK11 leading to the phosphorylation of both proteins and excluding STK11 from the nucleus. The protein is necessary for STK11-induced G1 cell cycle arrest. A mutation in this gene has been shown to result in polyhydramnios, megalencephaly, and symptomatic epilepsy (PMSE) syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. Additional transcript variants have been described but their full-length nature is not known. [provided by RefSeq, Sep 2009]

STRADA Gene-Disease associations (from GenCC):

polyhydramnios, megalencephaly, and symptomatic epilepsy
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P

STRADA links:

ENSG00000125695 (HGNC:):

ENSG00000125695 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 17-63728319-T-C is Benign according to our data. Variant chr17-63728319-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 377300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00452 (688/152180) while in subpopulation AMR AF = 0.0147 (225/15272). AF 95% confidence interval is 0.0132. There are 8 homozygotes in GnomAd4. There are 464 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003787.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
STRADA	NM_001003787.4	MANE Select	c.36+15A>G	intron	N/A	NP_001003787.1
STRADA	NM_001363786.1		c.12+39A>G	intron	N/A	NP_001350715.1
STRADA	NM_001363787.1		c.36+15A>G	intron	N/A	NP_001350716.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
STRADA	ENST00000336174.12	TSL:1 MANE Select	c.36+15A>G	intron	N/A	ENSP00000336655.6
STRADA	ENST00000375840.9	TSL:1	c.-110+15A>G	intron	N/A	ENSP00000365000.4
STRADA	ENST00000392950.9	TSL:1	c.12+39A>G	intron	N/A	ENSP00000376677.4

Frequencies

GnomAD3 genomes

AF:

0.00452

AC:

687

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0148

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.0117

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.0327

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00812

AC:

2033

AN:

250284

AF XY:

0.00674

show subpopulations

Gnomad AFR exome

AF:

0.000310

Gnomad AMR exome

AF:

0.0318

Gnomad ASJ exome

AF:

0.000993

Gnomad EAS exome

AF:

0.00993

Gnomad FIN exome

AF:

0.0309

Gnomad NFE exome

AF:

0.000353

Gnomad OTH exome

AF:

0.00524

GnomAD4 exome

AF:

0.00253

AC:

3692

AN:

1460704

Hom.:

Cov.:

AF XY:

0.00230

AC XY:

1674

AN XY:

726708

show subpopulations

African (AFR)

AF:

0.000389

AC:

AN:

33410

American (AMR)

AF:

0.0291

AC:

1295

AN:

44560

Ashkenazi Jewish (ASJ)

AF:

0.000842

AC:

AN:

26118

East Asian (EAS)

AF:

0.0174

AC:

690

AN:

39620

South Asian (SAS)

AF:

0.000499

AC:

AN:

86152

European-Finnish (FIN)

AF:

0.0267

AC:

1417

AN:

53140

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000109

AC:

121

AN:

1111582

Other (OTH)

AF:

0.00149

AC:

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

166

332

497

663

829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00452

AC:

688

AN:

152180

Hom.:

Cov.:

AF XY:

0.00624

AC XY:

464

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.000433

AC:

AN:

41530

American (AMR)

AF:

0.0147

AC:

225

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.0120

AC:

AN:

5186

South Asian (SAS)

AF:

0.000622

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0327

AC:

346

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000412

AC:

AN:

67990

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

105

140

175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00222

Hom.:

Bravo

AF:

0.00389

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Polyhydramnios, megalencephaly, and symptomatic epilepsy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

0.17

PromoterAI

0.0019

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over