rs875659

Positions:

• chr7-102266376-G-A
• chr7-102266376-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001913.5(CUX1):​c.1256-6990G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,466 control chromosomes in the GnomAD database, including 18,159 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 0.47 (18159 hom., cov: 28)
• Consequence: CUX1 NM_001913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.464

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUX1	NM_001913.5	c.1256-6990G>A		intron_variant		ENST00000622516.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUX1	ENST00000622516.6	c.1256-6990G>A		intron_variant		1	NM_001913.5

Frequencies

GnomAD3 genomes AF: 0.475 AC: 71844 AN: 151350 Hom.: 18150 Cov.: 28

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.475 AC: 71879 AN: 151466 Hom.: 18159 Cov.: 28 AF XY: 0.478 AC XY: 35353 AN XY: 73964

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.516

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.501

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.473

Alfa AF: 0.521 Hom.: 17609

Bravo AF: 0.465

Asia WGS AF: 0.605 AC: 2101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.23
DANN	Benign	0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs875659; hg19: chr7-101909656;