rs365836

Positions:

• chr7-102166571-A-G

Variant summary

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

The NM_181552.4(CUX1):​c.724-3875A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,024 control chromosomes in the GnomAD database, including 8,431 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 0.31 (8431 hom., cov: 31)
• Consequence: CUX1 NM_181552.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69

Genes affected

CUX1 (HGNC:2557): (cut like homeobox 1) The protein encoded by this gene is a member of the homeodomain family of DNA binding proteins. It may regulate gene expression, morphogenesis, and differentiation and it may also play a role in the cell cycle progession. Several alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUX1	NM_001913.5	c.757-3875A>G		intron_variant		ENST00000622516.6	NP_001904.2
CUX1	NM_181552.4	c.724-3875A>G		intron_variant		ENST00000292535.12	NP_853530.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUX1	ENST00000292535.12	c.724-3875A>G		intron_variant		1	NM_181552.4	ENSP00000292535	A2
CUX1	ENST00000622516.6	c.757-3875A>G		intron_variant		1	NM_001913.5	ENSP00000484760

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47730 AN: 151906 Hom.: 8414 Cov.: 31

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.0828

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.314 AC: 47799 AN: 152024 Hom.: 8431 Cov.: 31 AF XY: 0.309 AC XY: 22932 AN XY: 74308

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.0832

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.309

Alfa AF: 0.267 Hom.: 8627

Bravo AF: 0.326

Asia WGS AF: 0.192 AC: 673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0030
DANN	Benign	0.25

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: rs365836; hg19: chr7-101809851;