20-56454702-T-C

Position:

• chr20-56454702-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.1953+1573T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 152,100 control chromosomes in the GnomAD database, including 30,709 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 0.63 (30709 hom., cov: 32)
• Consequence: CASS4 NM_020356.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASS4	NM_020356.4	c.1953+1573T>C		intron_variant		ENST00000679887.1	NP_065089.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASS4	ENST00000679887.1	c.1953+1573T>C		intron_variant			NM_020356.4	ENSP00000506506.1
CASS4	ENST00000360314.7	c.1953+1573T>C		intron_variant		1		ENSP00000353462.3
CASS4	ENST00000679529.1	c.1791+1573T>C		intron_variant				ENSP00000505834.1
CASS4	ENST00000434344.2	c.643-3638T>C		intron_variant		2		ENSP00000410027.1

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95417 AN: 151982 Hom.: 30674 Cov.: 32

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.652

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

GnomAD4 genome AF: 0.628 AC: 95505 AN: 152100 Hom.: 30709 Cov.: 32 AF XY: 0.631 AC XY: 46903 AN XY: 74338

Gnomad4 AFR AF: 0.700

Gnomad4 AMR AF: 0.657

Gnomad4 ASJ AF: 0.724

Gnomad4 EAS AF: 0.943

Gnomad4 SAS AF: 0.676

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.653

Alfa AF: 0.525 Hom.: 2597

Bravo AF: 0.645

Asia WGS AF: 0.805 AC: 2796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.1
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs401897; hg19: chr20-55029758;