rs4811697

Positions:

• chr20-56458800-A-C
• chr20-56458800-A-G
• chr20-56458800-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASS4	NM_020356.4	c.*53A>C		3_prime_UTR_variant	6/6	ENST00000679887.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASS4	ENST00000679887.1	c.*53A>C		3_prime_UTR_variant	6/6		NM_020356.4	P2
CASS4	ENST00000434344.2	c.*53A>C		3_prime_UTR_variant	5/5	2
CASS4	ENST00000679529.1	c.*53A>C		3_prime_UTR_variant	6/6			A2
CASS4	ENST00000360314.7			downstream_gene_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61115 AN: 151734 Hom.: 13336 Cov.: 31

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.: 24 AF XY: 0.367 AC XY: 238339 AN XY: 648650

Gnomad4 AFR exome AF: 0.407

Gnomad4 AMR exome AF: 0.578

Gnomad4 ASJ exome AF: 0.417

Gnomad4 EAS exome AF: 0.944

Gnomad4 SAS exome AF: 0.478

Gnomad4 FIN exome AF: 0.376

Gnomad4 NFE exome AF: 0.326

Gnomad4 OTH exome AF: 0.396

GnomAD4 genome AF: 0.403 AC: 61168 AN: 151852 Hom.: 13348 Cov.: 31 AF XY: 0.412 AC XY: 30589 AN XY: 74186

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.934

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.425

Alfa AF: 0.348 Hom.: 9324

Bravo AF: 0.417

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.31
DANN	Benign	0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4811697; hg19: chr20-55033856;