5-131296962-C-G

Variant names:

• chr5-131296962-C-G
• rs1030271
• NM_001375635.1:c.-454-19014C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375635.1(CDC42SE2):​c.-454-19014C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 151,824 control chromosomes in the GnomAD database, including 5,846 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 0.24 (5846 hom., cov: 31)
• Consequence: CDC42SE2 NM_001375635.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100
• Publications: 8 publications found

Genes affected

CDC42SE2 (HGNC:18547): (CDC42 small effector 2) Enables signaling adaptor activity. Involved in regulation of signal transduction. Located in plasma membrane. [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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC42SE2	NM_001375635.1	c.-454-19014C>G		intron_variant	Intron 1 of 4	ENST00000505065.2	NP_001362564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC42SE2	ENST00000505065.2	c.-454-19014C>G		intron_variant	Intron 1 of 4	1	NM_001375635.1	ENSP00000427421.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36595 AN: 151706 Hom.: 5848 Cov.: 31

Gnomad AFR AF: 0.0686

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.0919

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.241 AC: 36587 AN: 151824 Hom.: 5846 Cov.: 31 AF XY: 0.230 AC XY: 17066 AN XY: 74170

African (AFR) AF: 0.0684 AC: 2834 AN: 41448

American (AMR) AF: 0.253 AC: 3852 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 820 AN: 3458

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5176

South Asian (SAS) AF: 0.0916 AC: 440 AN: 4806

European-Finnish (FIN) AF: 0.258 AC: 2694 AN: 10442

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24886 AN: 67942

Other (OTH) AF: 0.274 AC: 578 AN: 2106

Alfa AF: 0.279 Hom.: 815

Bravo AF: 0.238

Asia WGS AF: 0.0460 AC: 161 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.45
PhyloP100		0.10
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: rs1030271; hg19: chr5-130632655; COSMIC: COSV64759193;