dbSNP rs4811697: CASS4:c.*53A>C (chr20-56458800-A-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.*53A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 1,481,016 control chromosomes in the GnomAD database, including 110,999 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 0.40 ( 13348 hom., cov: 31)

Exomes 𝑓: 0.37 ( 97651 hom. )

Consequence

CASS4
NM_020356.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.33

Publications

9 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:

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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=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020356.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CASS4	NM_020356.4	MANE Select	c.*53A>C	3_prime_UTR	Exon 6 of 6	NP_065089.2
CASS4	NM_001164116.2		c.*53A>C	3_prime_UTR	Exon 7 of 7	NP_001157588.1
CASS4	NM_001164114.2		c.*53A>C	3_prime_UTR	Exon 6 of 6	NP_001157586.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CASS4	ENST00000679887.1	MANE Select	c.*53A>C	3_prime_UTR	Exon 6 of 6	ENSP00000506506.1
CASS4	ENST00000679529.1		c.*53A>C	3_prime_UTR	Exon 6 of 6	ENSP00000505834.1
CASS4	ENST00000434344.2	TSL:2	c.*53A>C	3_prime_UTR	Exon 5 of 5	ENSP00000410027.1

Frequencies

GnomAD3 genomes

AF:

0.403

AC:

61115

AN:

151734

Hom.:

13336

Cov.:

show subpopulations

Gnomad AFR

AF:

0.411

Gnomad AMI

AF:

0.511

Gnomad AMR

AF:

0.476

Gnomad ASJ

AF:

0.412

Gnomad EAS

AF:

0.934

Gnomad SAS

AF:

0.481

Gnomad FIN

AF:

0.402

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.422

GnomAD4 exome

AF:

0.365

AC:

485701

AN:

1329164

Hom.:

97651

Cov.:

AF XY:

0.367

AC XY:

238339

AN XY:

648650

show subpopulations

African (AFR)

AF:

0.407

AC:

12432

AN:

30570

American (AMR)

AF:

0.578

AC:

18314

AN:

31698

Ashkenazi Jewish (ASJ)

AF:

0.417

AC:

8838

AN:

21216

East Asian (EAS)

AF:

0.944

AC:

33791

AN:

35812

South Asian (SAS)

AF:

0.478

AC:

34056

AN:

71224

European-Finnish (FIN)

AF:

0.376

AC:

17700

AN:

47086

Middle Eastern (MID)

AF:

0.453

AC:

1700

AN:

3752

European-Non Finnish (NFE)

AF:

0.326

AC:

337057

AN:

1032776

Other (OTH)

AF:

0.396

AC:

21813

AN:

55030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

14130

28260

42391

56521

70651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11618

23236

34854

46472

58090

<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:

0.403

AC:

61168

AN:

151852

Hom.:

13348

Cov.:

AF XY:

0.412

AC XY:

30589

AN XY:

74186

show subpopulations

African (AFR)

AF:

0.411

AC:

17008

AN:

41394

American (AMR)

AF:

0.477

AC:

7270

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.412

AC:

1427

AN:

3462

East Asian (EAS)

AF:

0.934

AC:

4804

AN:

5142

South Asian (SAS)

AF:

0.482

AC:

2322

AN:

4820

European-Finnish (FIN)

AF:

0.402

AC:

4238

AN:

10544

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.333

AC:

22610

AN:

67932

Other (OTH)

AF:

0.425

AC:

896

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1812

3625

5437

7250

9062

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

580

1160

1740

2320

2900

<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:

0.357

Hom.:

12934

Bravo

AF:

0.417

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.31

(source)

DANN

Benign

0.54

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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