7-102070310-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_181552.4(CUX1):c.190-29T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 1,582,904 control chromosomes in the GnomAD database, including 550,877 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.84 (53548 hom., cov: 33)
  • Exomes 𝑓: 0.83 (497329 hom.)
• Consequence: CUX1 NM_181552.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.231

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 7-102070310-T-C is Benign according to our data. Variant chr7-102070310-T-C is described in ClinVar as [Benign]. Clinvar id is 1255424.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUX1	NM_001913.5	c.223-29T>C		intron_variant		ENST00000622516.6
CUX1	NM_181552.4	c.190-29T>C		intron_variant		ENST00000292535.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUX1	ENST00000292535.12	c.190-29T>C		intron_variant		1	NM_181552.4	A2
CUX1	ENST00000622516.6	c.223-29T>C		intron_variant		1	NM_001913.5

Frequencies

GnomAD3 genomes AF: 0.838 AC: 127409 AN: 152064 Hom.: 53517 Cov.: 33

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.848

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.875

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.821

GnomAD3 exomes AF: 0.854 AC: 205620 AN: 240842 Hom.: 88189 AF XY: 0.851 AC XY: 111663 AN XY: 131234

Gnomad AFR exome AF: 0.842

Gnomad AMR exome AF: 0.901

Gnomad ASJ exome AF: 0.778

Gnomad EAS exome AF: 0.991

Gnomad SAS exome AF: 0.869

Gnomad FIN exome AF: 0.883

Gnomad NFE exome AF: 0.819

Gnomad OTH exome AF: 0.822

GnomAD4 exome AF: 0.833 AC: 1191130 AN: 1430722 Hom.: 497329 Cov.: 24 AF XY: 0.833 AC XY: 594143 AN XY: 713526

Gnomad4 AFR exome AF: 0.846

Gnomad4 AMR exome AF: 0.895

Gnomad4 ASJ exome AF: 0.775

Gnomad4 EAS exome AF: 0.992

Gnomad4 SAS exome AF: 0.870

Gnomad4 FIN exome AF: 0.881

Gnomad4 NFE exome AF: 0.820

Gnomad4 OTH exome AF: 0.833

GnomAD4 genome AF: 0.838 AC: 127492 AN: 152182 Hom.: 53548 Cov.: 33 AF XY: 0.842 AC XY: 62647 AN XY: 74390

Gnomad4 AFR AF: 0.842

Gnomad4 AMR AF: 0.849

Gnomad4 ASJ AF: 0.770

Gnomad4 EAS AF: 0.991

Gnomad4 SAS AF: 0.874

Gnomad4 FIN AF: 0.879

Gnomad4 NFE AF: 0.818

Gnomad4 OTH AF: 0.824

Alfa AF: 0.796 Hom.: 5668

Bravo AF: 0.838

Asia WGS AF: 0.916 AC: 3186 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Global developmental delay with or without impaired intellectual development Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	16
Dann	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs377612; hg19: chr7-101713590;