rs201522

Positions:

• chr7-102128266-G-A

Variant summary

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

The NM_181552.4(CUX1):​c.674+12993G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 152,066 control chromosomes in the GnomAD database, including 28,874 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 0.61 (28874 hom., cov: 32)
• Consequence: CUX1 NM_181552.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUX1	NM_001913.5	c.707+12993G>A		intron_variant		ENST00000622516.6
CUX1	NM_181552.4	c.674+12993G>A		intron_variant		ENST00000292535.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUX1	ENST00000292535.12	c.674+12993G>A		intron_variant		1	NM_181552.4	A2
CUX1	ENST00000622516.6	c.707+12993G>A		intron_variant		1	NM_001913.5

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91937 AN: 151946 Hom.: 28843 Cov.: 32

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.0964

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.604

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

GnomAD4 genome AF: 0.605 AC: 92025 AN: 152066 Hom.: 28874 Cov.: 32 AF XY: 0.598 AC XY: 44475 AN XY: 74342

Gnomad4 AFR AF: 0.713

Gnomad4 AMR AF: 0.558

Gnomad4 ASJ AF: 0.697

Gnomad4 EAS AF: 0.0968

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.605

Alfa AF: 0.598 Hom.: 13391

Bravo AF: 0.610

Asia WGS AF: 0.391 AC: 1362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.010
DANN	Benign	0.47

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: rs201522; hg19: chr7-101771546;