chr7-102270864-C-T

Variant names:

• chr7-102270864-C-T
• rs1725604
• NM_001913.5:c.1256-2502C>T

Variant summary

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

The NM_001913.5(CUX1):​c.1256-2502C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 152,070 control chromosomes in the GnomAD database, including 29,924 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 0.62 (29924 hom., cov: 32)
• Consequence: CUX1 NM_001913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640
• Publications: 10 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001913.5. 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_001913.5	MANE Plus Clinical	c.1256-2502C>T		intron	N/A	NP_001904.2
	CUX1	NM_181500.4		c.1250-2502C>T		intron	N/A	NP_852477.1
	CUX1	NM_001202544.3		c.1208-2502C>T		intron	N/A	NP_001189473.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUX1	ENST00000622516.6	TSL:1 MANE Plus Clinical	c.1256-2502C>T		intron	N/A	ENSP00000484760.2
	CUX1	ENST00000292538.9	TSL:1	c.1256-2502C>T		intron	N/A	ENSP00000292538.4
	CUX1	ENST00000437600.9	TSL:1	c.1250-2502C>T		intron	N/A	ENSP00000414091.5

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94821 AN: 151952 Hom.: 29887 Cov.: 32

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.642

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.604

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

GnomAD4 genome AF: 0.624 AC: 94914 AN: 152070 Hom.: 29924 Cov.: 32 AF XY: 0.617 AC XY: 45882 AN XY: 74328

African (AFR) AF: 0.734 AC: 30437 AN: 41466

American (AMR) AF: 0.576 AC: 8794 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2194 AN: 3472

East Asian (EAS) AF: 0.504 AC: 2603 AN: 5168

South Asian (SAS) AF: 0.593 AC: 2860 AN: 4824

European-Finnish (FIN) AF: 0.526 AC: 5572 AN: 10588

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40410 AN: 67964

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

Alfa AF: 0.608 Hom.: 21821

Bravo AF: 0.637

Asia WGS AF: 0.610 AC: 2120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.27
DANN	Benign	0.49
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1725604; hg19: chr7-101914135;