dbSNP rs16979934: CASS4:c.643-96T>C (chr20-56451723-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_020356.4(CASS4):c.643-96T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0524 in 886,538 control chromosomes in the GnomAD database, including 1,297 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 0.055 ( 259 hom., cov: 32)

Exomes 𝑓: 0.052 ( 1038 hom. )

Consequence

CASS4
NM_020356.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.819

Publications

7 publications found

Variant links:

Genes affected

CASS4 (HGNC:15878): (Cas scaffold protein family member 4) Enables protein tyrosine kinase binding activity. Involved in several processes, including positive regulation of protein kinase B signaling; positive regulation of protein tyrosine kinase activity; and positive regulation of substrate adhesion-dependent cell spreading. Located in focal adhesion. Part of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CASS4 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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASS4	NM_020356.4 link	c.643-96T>C		intron_variant	Intron 4 of 5	ENST00000679887.1	NP_065089.2	Q9NQ75-1B4DII4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASS4	ENST00000679887.1 link	c.643-96T>C		intron_variant	Intron 4 of 5		NM_020356.4	ENSP00000506506.1		Q9NQ75-1

Frequencies

GnomAD3 genomes

AF:

0.0554

AC:

8426

AN:

152118

Hom.:

261

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0763

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.0393

Gnomad ASJ

AF:

0.0415

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0555

Gnomad FIN

AF:

0.0355

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0545

Gnomad OTH

AF:

0.0555

GnomAD4 exome

AF:

0.0518

AC:

38010

AN:

734302

Hom.:

1038

AF XY:

0.0522

AC XY:

19813

AN XY:

379260

show subpopulations

African (AFR)

AF:

0.0757

AC:

1368

AN:

18072

American (AMR)

AF:

0.0308

AC:

811

AN:

26326

Ashkenazi Jewish (ASJ)

AF:

0.0432

AC:

692

AN:

16018

East Asian (EAS)

AF:

0.000309

AC:

AN:

35566

South Asian (SAS)

AF:

0.0590

AC:

3244

AN:

54972

European-Finnish (FIN)

AF:

0.0381

AC:

1811

AN:

47490

Middle Eastern (MID)

AF:

0.0639

AC:

163

AN:

2552

European-Non Finnish (NFE)

AF:

0.0561

AC:

27930

AN:

497866

Other (OTH)

AF:

0.0559

AC:

1980

AN:

35440

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1853

3707

5560

7414

9267

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

698

1396

2094

2792

3490

<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:

0.0554

AC:

8431

AN:

152236

Hom.:

259

Cov.:

AF XY:

0.0544

AC XY:

4048

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0765

AC:

3175

AN:

41524

American (AMR)

AF:

0.0392

AC:

600

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0415

AC:

144

AN:

3466

East Asian (EAS)

AF:

0.000386

AC:

AN:

5178

South Asian (SAS)

AF:

0.0547

AC:

264

AN:

4826

European-Finnish (FIN)

AF:

0.0355

AC:

377

AN:

10616

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0545

AC:

3707

AN:

68012

Other (OTH)

AF:

0.0540

AC:

114

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

405

810

1216

1621

2026

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<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:

0.0524

Hom.:

375

Bravo

AF:

0.0560

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.073

(source)

DANN

Benign

0.52

PhyloP100

-0.82

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over