chr7-102070310-T-G

Variant names:

• chr7-102070310-T-G
• rs377612
• NM_181552.4:c.190-29T>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_181552.4(CUX1):​c.190-29T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000419 in 1,432,196 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: CUX1 NM_181552.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.231
• Publications: 3 publications found

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]

CUX1 Gene-Disease associations (from GenCC):

• global developmental delay with or without impaired intellectual development

  Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181552.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUX1	NM_181552.4	MANE Select	c.190-29T>G		intron	N/A	NP_853530.2	P39880-1
	CUX1	NM_001913.5	MANE Plus Clinical	c.223-29T>G		intron	N/A	NP_001904.2
	CUX1	NM_001202543.2		c.223-29T>G		intron	N/A	NP_001189472.1	P39880-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUX1	ENST00000292535.12	TSL:1 MANE Select	c.190-29T>G		intron	N/A	ENSP00000292535.7	P39880-1
	CUX1	ENST00000622516.6	TSL:1 MANE Plus Clinical	c.223-29T>G		intron	N/A	ENSP00000484760.2	Q13948-1
	CUX1	ENST00000360264.7	TSL:1	c.223-29T>G		intron	N/A	ENSP00000353401.3	P39880-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000125 AC: 3 AN: 240842 AF XY: 0.0000152

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000271

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000419 AC: 6 AN: 1432196 Hom.: 0 Cov.: 24 AF XY: 0.00000560 AC XY: 4 AN XY: 714202

African (AFR) AF: 0.00 AC: 0 AN: 32856

American (AMR) AF: 0.00 AC: 0 AN: 44026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25960

East Asian (EAS) AF: 0.00 AC: 0 AN: 39476

South Asian (SAS) AF: 0.00 AC: 0 AN: 85246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4372

European-Non Finnish (NFE) AF: 0.00000549 AC: 6 AN: 1093228

Other (OTH) AF: 0.00 AC: 0 AN: 59412

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 5929

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.85
PhyloP100		0.23

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

Other links and lift over

dbSNP: rs377612; hg19: chr7-101713590;