20-56454702-T-C

Variant names:

• chr20-56454702-T-C
• rs401897
• NM_020356.4:c.1953+1573T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CASS4	NM_020356.4	c.1953+1573T>C		intron_variant	Intron 5 of 5	ENST00000679887.1	NP_065089.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASS4	ENST00000679887.1	c.1953+1573T>C		intron_variant	Intron 5 of 5		NM_020356.4	ENSP00000506506.1
CASS4	ENST00000360314.7	c.1953+1573T>C		intron_variant	Intron 6 of 6	1		ENSP00000353462.3
CASS4	ENST00000679529.1	c.1791+1573T>C		intron_variant	Intron 5 of 5			ENSP00000505834.1
CASS4	ENST00000434344.2	c.643-3638T>C		intron_variant	Intron 4 of 4	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

African (AFR) AF: 0.700 AC: 29024 AN: 41480

American (AMR) AF: 0.657 AC: 10045 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 2511 AN: 3468

East Asian (EAS) AF: 0.943 AC: 4881 AN: 5176

South Asian (SAS) AF: 0.676 AC: 3265 AN: 4828

European-Finnish (FIN) AF: 0.554 AC: 5860 AN: 10572

Middle Eastern (MID) AF: 0.695 AC: 203 AN: 292

European-Non Finnish (NFE) AF: 0.556 AC: 37780 AN: 67978

Other (OTH) AF: 0.653 AC: 1379 AN: 2112

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
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs401897; hg19: chr20-55029758;