20-56443204-T-C

Variant summary

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

The NM_020356.4(CASS4):c.460-2696T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 151,216 control chromosomes in the GnomAD database, including 1,571 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 0.11 (1571 hom., cov: 31)
• Consequence: CASS4 NM_020356.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.683

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASS4	NM_020356.4	c.460-2696T>C		intron_variant		ENST00000679887.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASS4	ENST00000679887.1	c.460-2696T>C		intron_variant			NM_020356.4	P2

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17333 AN: 151100 Hom.: 1560 Cov.: 31

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0936

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0231

Gnomad FIN AF: 0.0246

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0852

Gnomad OTH AF: 0.124

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.115 AC: 17375 AN: 151216 Hom.: 1571 Cov.: 31 AF XY: 0.110 AC XY: 8105 AN XY: 73896

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.0934

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.0231

Gnomad4 FIN AF: 0.0246

Gnomad4 NFE AF: 0.0852

Gnomad4 OTH AF: 0.122

Alfa AF: 0.0944 Hom.: 340

Bravo AF: 0.125

Asia WGS AF: 0.0290 AC: 102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.83
Dann	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7274581; hg19: chr20-55018260;