rs6024870

chr20-56422512-G-Achr20-56422512-G-C

Variant summary

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

The NM_020356.4(CASS4):c.36+10018G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.079 in 152,268 control chromosomes in the GnomAD database, including 559 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 0.079 (559 hom., cov: 33)
• Consequence: CASS4 NM_020356.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.136

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASS4	NM_020356.4	c.36+10018G>A		intron_variant		ENST00000679887.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASS4	ENST00000679887.1	c.36+10018G>A		intron_variant			NM_020356.4	P2

Frequencies

GnomAD3 genomes AF: 0.0791 AC: 12028 AN: 152150 Hom.: 561 Cov.: 33

Gnomad AFR AF: 0.0871

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0812

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.0227

Gnomad FIN AF: 0.0244

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0863

Gnomad OTH AF: 0.0966

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

GnomAD4 genome AF: 0.0790 AC: 12032 AN: 152268 Hom.: 559 Cov.: 33 AF XY: 0.0756 AC XY: 5626 AN XY: 74452

Gnomad4 AFR AF: 0.0871

Gnomad4 AMR AF: 0.0810

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.0228

Gnomad4 FIN AF: 0.0244

Gnomad4 NFE AF: 0.0863

Gnomad4 OTH AF: 0.0951

Alfa AF: 0.0581 Hom.: 69

Bravo AF: 0.0838

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.9
Dann	Benign	0.67

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: rs6024870; hg19: chr20-54997568;