7-102097326-T-G

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.269-38T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 1,577,430 control chromosomes in the GnomAD database, including 261,007 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.61 (29714 hom., cov: 32)
  • Exomes 𝑓: 0.56 (231293 hom.)
• Consequence: CUX1 NM_181552.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0570

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=-0.93).
• BP6: Variant 7-102097326-T-G is Benign according to our data. Variant chr7-102097326-T-G is described in ClinVar as [Benign]. Clinvar id is 1255425.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUX1	NM_001913.5	c.302-38T>G		intron_variant		ENST00000622516.6
CUX1	NM_181552.4	c.269-38T>G		intron_variant		ENST00000292535.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUX1	ENST00000292535.12	c.269-38T>G		intron_variant		1	NM_181552.4	A2
CUX1	ENST00000622516.6	c.302-38T>G		intron_variant		1	NM_001913.5

Frequencies

GnomAD3 genomes AF: 0.606 AC: 91758 AN: 151486 Hom.: 29673 Cov.: 32

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.0491

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.670

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.595

GnomAD3 exomes AF: 0.518 AC: 115524 AN: 222864 Hom.: 33083 AF XY: 0.520 AC XY: 62730 AN XY: 120634

Gnomad AFR exome AF: 0.799

Gnomad AMR exome AF: 0.407

Gnomad ASJ exome AF: 0.644

Gnomad EAS exome AF: 0.0496

Gnomad SAS exome AF: 0.477

Gnomad FIN exome AF: 0.504

Gnomad NFE exome AF: 0.582

Gnomad OTH exome AF: 0.555

GnomAD4 exome AF: 0.559 AC: 796572 AN: 1425830 Hom.: 231293 Cov.: 35 AF XY: 0.556 AC XY: 393765 AN XY: 707892

Gnomad4 AFR exome AF: 0.807

Gnomad4 AMR exome AF: 0.415

Gnomad4 ASJ exome AF: 0.643

Gnomad4 EAS exome AF: 0.0480

Gnomad4 SAS exome AF: 0.478

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.581

Gnomad4 OTH exome AF: 0.557

GnomAD4 genome AF: 0.606 AC: 91858 AN: 151600 Hom.: 29714 Cov.: 32 AF XY: 0.595 AC XY: 44071 AN XY: 74098

Gnomad4 AFR AF: 0.793

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.0496

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.596

Alfa AF: 0.520 Hom.: 2802

Bravo AF: 0.613

Asia WGS AF: 0.308 AC: 1075 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	3.3
Dann	Benign	0.56

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: rs1637257; hg19: chr7-101740606; COSMIC: COSV52900136; COSMIC: COSV52900136;