7-102104358-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_181552.4(CUX1):c.429A>G(p.Lys143=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000632 in 1,609,916 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00093 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00060 (1 hom.)
• Consequence: CUX1 NM_181552.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.15

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 7-102104358-A-G is Benign according to our data. Variant chr7-102104358-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2657859.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.15 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000934 (142/152090) while in subpopulation NFE AF= 0.001 (68/68010). AF 95% confidence interval is 0.000808. There are 1 homozygotes in gnomad4. There are 68 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 142 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUX1	NM_181552.4	c.429A>G	p.Lys143=	synonymous_variant	6/24	ENST00000292535.12
CUX1	NM_001913.5	c.462A>G	p.Lys154=	synonymous_variant	6/23	ENST00000622516.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUX1	ENST00000292535.12	c.429A>G	p.Lys143=	synonymous_variant	6/24	1	NM_181552.4	A2
CUX1	ENST00000622516.6	c.462A>G	p.Lys154=	synonymous_variant	6/23	1	NM_001913.5

Frequencies

GnomAD3 genomes AF: 0.000934 AC: 142 AN: 152090 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00100

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000372 AC: 92 AN: 247582 Hom.: 0 AF XY: 0.000395 AC XY: 53 AN XY: 134120

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000381

Gnomad NFE exome AF: 0.000661

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000600 AC: 875 AN: 1457826 Hom.: 1 Cov.: 33 AF XY: 0.000583 AC XY: 423 AN XY: 725422

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000400

Gnomad4 NFE exome AF: 0.000729

Gnomad4 OTH exome AF: 0.000613

GnomAD4 genome AF: 0.000934 AC: 142 AN: 152090 Hom.: 1 Cov.: 31 AF XY: 0.000915 AC XY: 68 AN XY: 74278

Gnomad4 AFR AF: 0.000169

Gnomad4 AMR AF: 0.0000656

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00100

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000589 Hom.: 0

Bravo AF: 0.00110

EpiCase AF: 0.00104

EpiControl AF: 0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

CUX1: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	9.7
Dann	Benign	0.65

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: rs201650660; hg19: chr7-101747638;