7-102104295-A-G

Variant names:

• chr7-102104295-A-G
• rs201480
• NM_181552.4:c.407-41A>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.407-41A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 1,559,028 control chromosomes in the GnomAD database, including 276,600 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 0.63 (31398 hom., cov: 31)
  • Exomes 𝑓: 0.58 (245202 hom.)
• Consequence: CUX1 NM_181552.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.350
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 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.407-41A>G		intron	N/A	NP_853530.2
	CUX1	NM_001913.5	MANE Plus Clinical	c.440-41A>G		intron	N/A	NP_001904.2
	CUX1	NM_001202543.2		c.440-41A>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.407-41A>G		intron	N/A	ENSP00000292535.7
	CUX1	ENST00000622516.6	TSL:1 MANE Plus Clinical	c.440-41A>G		intron	N/A	ENSP00000484760.2
	CUX1	ENST00000360264.7	TSL:1	c.440-41A>G		intron	N/A	ENSP00000353401.3

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95105 AN: 151508 Hom.: 31354 Cov.: 31

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.0960

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.622

GnomAD2 exomes AF: 0.557 AC: 124816 AN: 224130 AF XY: 0.559

Gnomad AFR exome AF: 0.798

Gnomad AMR exome AF: 0.512

Gnomad ASJ exome AF: 0.675

Gnomad EAS exome AF: 0.0958

Gnomad FIN exome AF: 0.521

Gnomad NFE exome AF: 0.596

Gnomad OTH exome AF: 0.588

GnomAD4 exome AF: 0.581 AC: 818072 AN: 1407398 Hom.: 245202 Cov.: 27 AF XY: 0.581 AC XY: 407253 AN XY: 701250

African (AFR) AF: 0.803 AC: 25125 AN: 31300

American (AMR) AF: 0.518 AC: 20332 AN: 39254

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 16866 AN: 25030

East Asian (EAS) AF: 0.0929 AC: 3636 AN: 39150

South Asian (SAS) AF: 0.576 AC: 47223 AN: 81928

European-Finnish (FIN) AF: 0.517 AC: 19898 AN: 38460

Middle Eastern (MID) AF: 0.686 AC: 3818 AN: 5568

European-Non Finnish (NFE) AF: 0.595 AC: 647163 AN: 1088514

Other (OTH) AF: 0.584 AC: 34011 AN: 58194

GnomAD4 genome AF: 0.628 AC: 95211 AN: 151630 Hom.: 31398 Cov.: 31 AF XY: 0.621 AC XY: 45958 AN XY: 74066

African (AFR) AF: 0.792 AC: 32749 AN: 41362

American (AMR) AF: 0.568 AC: 8657 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 2417 AN: 3468

East Asian (EAS) AF: 0.0966 AC: 499 AN: 5166

South Asian (SAS) AF: 0.555 AC: 2666 AN: 4804

European-Finnish (FIN) AF: 0.531 AC: 5512 AN: 10372

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40624 AN: 67912

Other (OTH) AF: 0.623 AC: 1313 AN: 2108

Alfa AF: 0.609 Hom.: 38887

Bravo AF: 0.636

Asia WGS AF: 0.395 AC: 1378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.71
DANN	Benign	0.53
PhyloP100		0.35
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: rs201480; hg19: chr7-101747575; COSMIC: COSV52897672; COSMIC: COSV52897672;