rs201522

Variant names:

• chr7-102128266-G-A
• rs201522
• NM_181552.4:c.674+12993G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

CUX1 Gene-Disease associations (from GenCC):

• global developmental delay with or without impaired intellectual development

  Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CUX1	NM_181552.4	c.674+12993G>A		intron_variant	Intron 8 of 23	ENST00000292535.12	NP_853530.2
CUX1	NM_001913.5	c.707+12993G>A		intron_variant	Intron 8 of 22	ENST00000622516.6	NP_001904.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUX1	ENST00000292535.12	c.674+12993G>A		intron_variant	Intron 8 of 23	1	NM_181552.4	ENSP00000292535.7
CUX1	ENST00000622516.6	c.707+12993G>A		intron_variant	Intron 8 of 22	1	NM_001913.5	ENSP00000484760.2

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

African (AFR) AF: 0.713 AC: 29559 AN: 41486

American (AMR) AF: 0.558 AC: 8527 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 2420 AN: 3472

East Asian (EAS) AF: 0.0968 AC: 501 AN: 5176

South Asian (SAS) AF: 0.555 AC: 2677 AN: 4820

European-Finnish (FIN) AF: 0.535 AC: 5660 AN: 10576

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40634 AN: 67952

Other (OTH) AF: 0.605 AC: 1275 AN: 2108

Alfa AF: 0.592 Hom.: 52727

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
PhyloP100		-0.60
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: rs201522; hg19: chr7-101771546;