Genetic Variant NM_138392.4: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

Publications

18 publications found

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 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

SHKBP1 links:

ENSG00000301801 (HGNC:):

ENSG00000301801 links:

Genome browser will be placed here

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138392.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHKBP1	NM_138392.4	MANE Select	c.1493-150A>G		intron	N/A	NP_612401.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SHKBP1	ENST00000291842.10	TSL:1 MANE Select	c.1493-150A>G	intron	N/A	ENSP00000291842.4
SHKBP1	ENST00000600733.5	TSL:5	c.1418-150A>G	intron	N/A	ENSP00000472711.1
SHKBP1	ENST00000600718.5	TSL:5	c.1474+153A>G	intron	N/A	ENSP00000471406.1

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

Age Distribution

Exome Het

Exome Hom

Variant carriers

11364

22728

34092

45456

56820

<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:

0.577

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

Age Distribution

Genome Het

Genome Hom

Variant carriers

726

1452

2178

2904

3630

<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:

0.522

Hom.:

59905

Bravo

AF:

0.586

Asia WGS

AF:

0.514

AC:

1788

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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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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