Genetic Variant SHKBP1:c.1493-150A>G (chr19-40588932-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_138392.4(SHKBP1):c.1493-150A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 1,264,686 control chromosomes in the GnomAD database, including 168,242 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.

Frequency

Genomes: 𝑓 0.58 ( 26619 hom., cov: 31)

Exomes 𝑓: 0.50 ( 141623 hom. )

Consequence

SHKBP1
NM_138392.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.654

Variant links:

Genes affected

SHKBP1 (HGNC:19214): (SH3KBP1 binding protein 1) Enables identical protein binding activity. Predicted to be involved in positive regulation of epidermal growth factor receptor signaling pathway. Predicted to be located in lysosome. [provided by Alliance of Genome Resources, Apr 2022]

SHKBP1 links:

ENSG00000301801 (HGNC:):

ENSG00000301801 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHKBP1	NM_138392.4 link	c.1493-150A>G		intron_variant	Intron 14 of 17	ENST00000291842.10	NP_612401.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHKBP1	ENST00000291842.10 link	c.1493-150A>G		intron_variant	Intron 14 of 17	1	NM_138392.4	ENSP00000291842.4		Q8TBC3-1

Frequencies

GnomAD3 genomes

AF:

0.577

AC:

87575

AN:

151848

Hom.:

26568

Cov.:

show subpopulations

Gnomad AFR

AF:

0.779

Gnomad AMI

AF:

0.389

Gnomad AMR

AF:

0.523

Gnomad ASJ

AF:

0.607

Gnomad EAS

AF:

0.405

Gnomad SAS

AF:

0.552

Gnomad FIN

AF:

0.539

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.489

Gnomad OTH

AF:

0.538

GnomAD4 exome

AF:

0.499

AC:

555763

AN:

1112720

Hom.:

141623

Cov.:

AF XY:

0.501

AC XY:

277793

AN XY:

554348

show subpopulations

African (AFR)

AF:

0.794

AC:

21104

AN:

26588

American (AMR)

AF:

0.533

AC:

17666

AN:

33170

Ashkenazi Jewish (ASJ)

AF:

0.598

AC:

12370

AN:

20694

East Asian (EAS)

AF:

0.374

AC:

12896

AN:

34508

South Asian (SAS)

AF:

0.555

AC:

37958

AN:

68332

European-Finnish (FIN)

AF:

0.527

AC:

17588

AN:

33374

Middle Eastern (MID)

AF:

0.519

AC:

2470

AN:

4756

European-Non Finnish (NFE)

AF:

0.484

AC:

408002

AN:

842798

Other (OTH)

AF:

0.530

AC:

25709

AN:

48500

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

14474

28949

43423

57898

72372

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.577

AC:

87689

AN:

151966

Hom.:

26619

Cov.:

AF XY:

0.577

AC XY:

42886

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.779

AC:

32298

AN:

41442

American (AMR)

AF:

0.523

AC:

7988

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.607

AC:

2102

AN:

3464

East Asian (EAS)

AF:

0.404

AC:

2083

AN:

5152

South Asian (SAS)

AF:

0.554

AC:

2669

AN:

4820

European-Finnish (FIN)

AF:

0.539

AC:

5683

AN:

10552

Middle Eastern (MID)

AF:

0.500

AC:

147

AN:

294

European-Non Finnish (NFE)

AF:

0.489

AC:

33232

AN:

67950

Other (OTH)

AF:

0.537

AC:

1133

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1794

3588

5381

7175

8969

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.522

Hom.:

59905

Bravo

AF:

0.586

Asia WGS

AF:

0.514

AC:

1788

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.4

(source)

DANN

Benign

0.49

PhyloP100

-0.65

PromoterAI

-0.0010

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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19-40588932-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over