rs6024870

Variant names:

• chr20-56422512-G-A
• rs6024870
• NM_020356.4:c.36+10018G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-56422512-G-A
• chr20-56422512-G-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.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
• Publications: 28 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0847 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020356.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASS4	NM_020356.4	MANE Select	c.36+10018G>A		intron	N/A	NP_065089.2
	CASS4	NM_001164116.2		c.36+10018G>A		intron	N/A	NP_001157588.1
	CASS4	NM_001164114.2		c.36+10018G>A		intron	N/A	NP_001157586.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASS4	ENST00000679887.1	MANE Select	c.36+10018G>A		intron	N/A	ENSP00000506506.1
	CASS4	ENST00000360314.7	TSL:1	c.36+10018G>A		intron	N/A	ENSP00000353462.3
	CASS4	ENST00000497244.1	TSL:1	n.187+10018G>A		intron	N/A

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

African (AFR) AF: 0.0871 AC: 3617 AN: 41530

American (AMR) AF: 0.0810 AC: 1239 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 599 AN: 3472

East Asian (EAS) AF: 0.000963 AC: 5 AN: 5190

South Asian (SAS) AF: 0.0228 AC: 110 AN: 4832

European-Finnish (FIN) AF: 0.0244 AC: 259 AN: 10604

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0863 AC: 5869 AN: 68018

Other (OTH) AF: 0.0951 AC: 201 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.9
DANN	Benign	0.67
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6024870; hg19: chr20-54997568;