chr7-102243424-A-G

Variant names:

• chr7-102243424-A-G
• rs427534
• NM_181552.4:c.3887+3840A>G

Variant summary

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

The NM_181552.4(CUX1):​c.3887+3840A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,820 control chromosomes in the GnomAD database, including 12,497 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 0.38 (12497 hom., cov: 30)
• Consequence: CUX1 NM_181552.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.268
• Publications: 9 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

LOC124901711 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181552.4. 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
	CUX1	NM_181552.4	MANE Select	c.3887+3840A>G		intron	N/A	NP_853530.2
	CUX1	NM_001913.5	MANE Plus Clinical	c.1256-29942A>G		intron	N/A	NP_001904.2
	CUX1	NM_001202543.2		c.3920+3840A>G		intron	N/A	NP_001189472.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUX1	ENST00000292535.12	TSL:1 MANE Select	c.3887+3840A>G		intron	N/A	ENSP00000292535.7
	CUX1	ENST00000622516.6	TSL:1 MANE Plus Clinical	c.1256-29942A>G		intron	N/A	ENSP00000484760.2
	CUX1	ENST00000360264.7	TSL:1	c.3920+3840A>G		intron	N/A	ENSP00000353401.3

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57858 AN: 151702 Hom.: 12498 Cov.: 30

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.381 AC: 57867 AN: 151820 Hom.: 12497 Cov.: 30 AF XY: 0.389 AC XY: 28887 AN XY: 74204

African (AFR) AF: 0.217 AC: 8978 AN: 41404

American (AMR) AF: 0.434 AC: 6617 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1055 AN: 3468

East Asian (EAS) AF: 0.880 AC: 4547 AN: 5166

South Asian (SAS) AF: 0.488 AC: 2349 AN: 4818

European-Finnish (FIN) AF: 0.492 AC: 5158 AN: 10490

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27907 AN: 67922

Other (OTH) AF: 0.392 AC: 827 AN: 2110

Alfa AF: 0.401 Hom.: 15318

Bravo AF: 0.372

Asia WGS AF: 0.621 AC: 2156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.70
PhyloP100		-0.27
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: rs427534; hg19: chr7-101886704;