rs16979934

chr20-56451723-T-Cchr20-56451723-T-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.819

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=-0.86).
• 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/exons	MANE	UniProt
CASS4	NM_020356.4	c.643-96T>C		intron_variant		ENST00000679887.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASS4	ENST00000679887.1	c.643-96T>C		intron_variant			NM_020356.4	P2

Frequencies

GnomAD3 genomes AF: 0.0554 AC: 8426 AN: 152118 Hom.: 261 Cov.: 32

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

Gnomad4 AFR exome AF: 0.0757

Gnomad4 AMR exome AF: 0.0308

Gnomad4 ASJ exome AF: 0.0432

Gnomad4 EAS exome AF: 0.000309

Gnomad4 SAS exome AF: 0.0590

Gnomad4 FIN exome AF: 0.0381

Gnomad4 NFE exome AF: 0.0561

Gnomad4 OTH exome AF: 0.0559

GnomAD4 genome AF: 0.0554 AC: 8431 AN: 152236 Hom.: 259 Cov.: 32 AF XY: 0.0544 AC XY: 4048 AN XY: 74450

Gnomad4 AFR AF: 0.0765

Gnomad4 AMR AF: 0.0392

Gnomad4 ASJ AF: 0.0415

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0547

Gnomad4 FIN AF: 0.0355

Gnomad4 NFE AF: 0.0545

Gnomad4 OTH AF: 0.0540

Alfa AF: 0.0511 Hom.: 209

Bravo AF: 0.0560

Asia WGS AF: 0.0270 AC: 94 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
Dann	Benign	0.52

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

LitVar

Other links and lift over

dbSNP: rs16979934; hg19: chr20-55026779;