7-102266376-G-A

Variant names:

• chr7-102266376-G-A
• rs875659
• NM_001913.5:c.1256-6990G>A

Variant summary

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

The NM_001913.5(CUX1):​c.1256-6990G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,466 control chromosomes in the GnomAD database, including 18,159 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 0.47 (18159 hom., cov: 28)
• Consequence: CUX1 NM_001913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.464
• Publications: 4 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

ENSG00000308634 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUX1	NM_001913.5	c.1256-6990G>A		intron_variant	Intron 14 of 22	ENST00000622516.6	NP_001904.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUX1	ENST00000622516.6	c.1256-6990G>A		intron_variant	Intron 14 of 22	1	NM_001913.5	ENSP00000484760.2

Frequencies

GnomAD3 genomes AF: 0.475 AC: 71844 AN: 151350 Hom.: 18150 Cov.: 28

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.475 AC: 71879 AN: 151466 Hom.: 18159 Cov.: 28 AF XY: 0.478 AC XY: 35353 AN XY: 73964

African (AFR) AF: 0.299 AC: 12360 AN: 41286

American (AMR) AF: 0.516 AC: 7825 AN: 15164

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1808 AN: 3470

East Asian (EAS) AF: 0.745 AC: 3802 AN: 5106

South Asian (SAS) AF: 0.501 AC: 2403 AN: 4796

European-Finnish (FIN) AF: 0.561 AC: 5868 AN: 10462

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36120 AN: 67876

Other (OTH) AF: 0.473 AC: 995 AN: 2104

Alfa AF: 0.517 Hom.: 20734

Bravo AF: 0.465

Asia WGS AF: 0.605 AC: 2101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.23
DANN	Benign	0.35
PhyloP100		-0.46
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: rs875659; hg19: chr7-101909656;