20-56451685-C-G

Position:

• chr20-56451685-C-G

Variant summary

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

The NM_020356.4(CASS4):​c.643-134C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 674,394 control chromosomes in the GnomAD database, including 61,260 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 0.48 (19341 hom., cov: 31)
  • Exomes 𝑓: 0.39 (41919 hom.)
• Consequence: CASS4 NM_020356.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASS4	NM_020356.4	c.643-134C>G		intron_variant		ENST00000679887.1	NP_065089.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASS4	ENST00000679887.1	c.643-134C>G		intron_variant			NM_020356.4	ENSP00000506506.1

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73131 AN: 151838 Hom.: 19293 Cov.: 31

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.423

GnomAD4 exome AF: 0.393 AC: 205316 AN: 522438 Hom.: 41919 AF XY: 0.389 AC XY: 106258 AN XY: 273438

Gnomad4 AFR exome AF: 0.710

Gnomad4 AMR exome AF: 0.441

Gnomad4 ASJ exome AF: 0.361

Gnomad4 EAS exome AF: 0.533

Gnomad4 SAS exome AF: 0.348

Gnomad4 FIN exome AF: 0.442

Gnomad4 NFE exome AF: 0.365

Gnomad4 OTH exome AF: 0.396

GnomAD4 genome AF: 0.482 AC: 73241 AN: 151956 Hom.: 19341 Cov.: 31 AF XY: 0.483 AC XY: 35846 AN XY: 74244

Gnomad4 AFR AF: 0.714

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.423

Alfa AF: 0.277 Hom.: 629

Bravo AF: 0.491

Asia WGS AF: 0.414 AC: 1442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.64

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: rs1884910; hg19: chr20-55026741;