7-102104295-A-G

Position:

• chr7-102104295-A-G

Variant summary

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

The NM_181552.4(CUX1):​c.407-41A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 1,559,028 control chromosomes in the GnomAD database, including 276,600 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 0.63 (31398 hom., cov: 31)
  • Exomes 𝑓: 0.58 (245202 hom.)
• Consequence: CUX1 NM_181552.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.350

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUX1	NM_001913.5	c.440-41A>G		intron_variant		ENST00000622516.6
CUX1	NM_181552.4	c.407-41A>G		intron_variant		ENST00000292535.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUX1	ENST00000292535.12	c.407-41A>G		intron_variant		1	NM_181552.4	A2
CUX1	ENST00000622516.6	c.440-41A>G		intron_variant		1	NM_001913.5

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95105 AN: 151508 Hom.: 31354 Cov.: 31

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.0960

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.622

GnomAD3 exomes AF: 0.557 AC: 124816 AN: 224130 Hom.: 37393 AF XY: 0.559 AC XY: 68573 AN XY: 122566

Gnomad AFR exome AF: 0.798

Gnomad AMR exome AF: 0.512

Gnomad ASJ exome AF: 0.675

Gnomad EAS exome AF: 0.0958

Gnomad SAS exome AF: 0.573

Gnomad FIN exome AF: 0.521

Gnomad NFE exome AF: 0.596

Gnomad OTH exome AF: 0.588

GnomAD4 exome AF: 0.581 AC: 818072 AN: 1407398 Hom.: 245202 Cov.: 27 AF XY: 0.581 AC XY: 407253 AN XY: 701250

Gnomad4 AFR exome AF: 0.803

Gnomad4 AMR exome AF: 0.518

Gnomad4 ASJ exome AF: 0.674

Gnomad4 EAS exome AF: 0.0929

Gnomad4 SAS exome AF: 0.576

Gnomad4 FIN exome AF: 0.517

Gnomad4 NFE exome AF: 0.595

Gnomad4 OTH exome AF: 0.584

GnomAD4 genome AF: 0.628 AC: 95211 AN: 151630 Hom.: 31398 Cov.: 31 AF XY: 0.621 AC XY: 45958 AN XY: 74066

Gnomad4 AFR AF: 0.792

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.697

Gnomad4 EAS AF: 0.0966

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.531

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.623

Alfa AF: 0.608 Hom.: 24844

Bravo AF: 0.636

Asia WGS AF: 0.395 AC: 1378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.71
DANN	Benign	0.53

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: rs201480; hg19: chr7-101747575; COSMIC: COSV52897672; COSMIC: COSV52897672;