rs2906724

Positions:

• chr7-101820749-C-A
• chr7-101820749-C-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	UniProt
CUX1	NM_001913.5	c.63+4656C>A		intron_variant		ENST00000622516.6
CUX1	NM_181552.4	c.30+3080C>A		intron_variant		ENST00000292535.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUX1	ENST00000292535.12	c.30+3080C>A		intron_variant		1	NM_181552.4	A2
CUX1	ENST00000622516.6	c.63+4656C>A		intron_variant		1	NM_001913.5

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

Gnomad4 AFR AF: 0.859

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.683

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.705

Alfa AF: 0.685 Hom.: 10430

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

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: rs2906724; hg19: chr7-101464029;