7-101820749-C-A

Variant names:

• chr7-101820749-C-A
• rs2906724
• NM_181552.4:c.30+3080C>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.30+3080C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,144 control chromosomes in the GnomAD database, including 40,851 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 0.73 (40851 hom., cov: 33)
• Consequence: CUX1 NM_181552.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910
• Publications: 1 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=-0.58).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUX1	NM_181552.4	c.30+3080C>A		intron_variant	Intron 1 of 23	ENST00000292535.12	NP_853530.2
CUX1	NM_001913.5	c.63+4656C>A		intron_variant	Intron 1 of 22	ENST00000622516.6	NP_001904.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUX1	ENST00000292535.12	c.30+3080C>A		intron_variant	Intron 1 of 23	1	NM_181552.4	ENSP00000292535.7
CUX1	ENST00000622516.6	c.63+4656C>A		intron_variant	Intron 1 of 22	1	NM_001913.5	ENSP00000484760.2

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110341 AN: 152026 Hom.: 40806 Cov.: 33

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.708

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

GnomAD4 genome AF: 0.726 AC: 110445 AN: 152144 Hom.: 40851 Cov.: 33 AF XY: 0.716 AC XY: 53249 AN XY: 74360

African (AFR) AF: 0.859 AC: 35671 AN: 41534

American (AMR) AF: 0.608 AC: 9296 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2263 AN: 3472

East Asian (EAS) AF: 0.591 AC: 3058 AN: 5172

South Asian (SAS) AF: 0.614 AC: 2965 AN: 4828

European-Finnish (FIN) AF: 0.683 AC: 7205 AN: 10548

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.705 AC: 47929 AN: 67996

Other (OTH) AF: 0.705 AC: 1490 AN: 2112

Alfa AF: 0.689 Hom.: 12381

Bravo AF: 0.728

Asia WGS AF: 0.618 AC: 2150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	9.7
DANN	Benign	0.79
PhyloP100		0.091
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: rs2906724; hg19: chr7-101464029;