rs1734879

Variant names:

• chr7-102097330-C-A
• rs1734879
• NM_181552.4:c.269-34C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-102097330-C-A
• chr7-102097330-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_181552.4(CUX1):​c.269-34C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 1,582,300 control chromosomes in the GnomAD database, including 261,486 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (29713 hom., cov: 32)
  • Exomes 𝑓: 0.56 (231773 hom.)
• Consequence: CUX1 NM_181552.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.775
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-102097330-C-A is Benign according to our data. Variant chr7-102097330-C-A is described in ClinVar as Benign. ClinVar VariationId is 1255426.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

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.269-34C>A		intron	N/A	NP_853530.2	P39880-1
	CUX1	NM_001913.5	MANE Plus Clinical	c.302-34C>A		intron	N/A	NP_001904.2
	CUX1	NM_001202543.2		c.302-34C>A		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.269-34C>A		intron	N/A	ENSP00000292535.7	P39880-1
	CUX1	ENST00000622516.6	TSL:1 MANE Plus Clinical	c.302-34C>A		intron	N/A	ENSP00000484760.2	Q13948-1
	CUX1	ENST00000360264.7	TSL:1	c.302-34C>A		intron	N/A	ENSP00000353401.3	P39880-3

Frequencies

GnomAD3 genomes AF: 0.606 AC: 91758 AN: 151460 Hom.: 29671 Cov.: 32

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.0486

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.594

GnomAD2 exomes AF: 0.517 AC: 117402 AN: 226910 AF XY: 0.519

Gnomad AFR exome AF: 0.799

Gnomad AMR exome AF: 0.405

Gnomad ASJ exome AF: 0.642

Gnomad EAS exome AF: 0.0495

Gnomad FIN exome AF: 0.503

Gnomad NFE exome AF: 0.582

Gnomad OTH exome AF: 0.555

GnomAD4 exome AF: 0.558 AC: 798941 AN: 1430724 Hom.: 231773 Cov.: 36 AF XY: 0.556 AC XY: 395057 AN XY: 710532

African (AFR) AF: 0.807 AC: 25664 AN: 31820

American (AMR) AF: 0.413 AC: 15486 AN: 37512

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 15756 AN: 24502

East Asian (EAS) AF: 0.0481 AC: 1895 AN: 39374

South Asian (SAS) AF: 0.479 AC: 38904 AN: 81302

European-Finnish (FIN) AF: 0.500 AC: 26340 AN: 52684

Middle Eastern (MID) AF: 0.663 AC: 3710 AN: 5592

European-Non Finnish (NFE) AF: 0.581 AC: 638315 AN: 1098954

Other (OTH) AF: 0.557 AC: 32871 AN: 58984

GnomAD4 genome AF: 0.606 AC: 91860 AN: 151576 Hom.: 29713 Cov.: 32 AF XY: 0.595 AC XY: 44088 AN XY: 74088

African (AFR) AF: 0.793 AC: 32749 AN: 41286

American (AMR) AF: 0.489 AC: 7456 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2319 AN: 3466

East Asian (EAS) AF: 0.0491 AC: 254 AN: 5172

South Asian (SAS) AF: 0.449 AC: 2152 AN: 4798

European-Finnish (FIN) AF: 0.514 AC: 5405 AN: 10512

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39522 AN: 67798

Other (OTH) AF: 0.596 AC: 1250 AN: 2098

Alfa AF: 0.600 Hom.: 9292

Bravo AF: 0.613

Asia WGS AF: 0.308 AC: 1075 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Global developmental delay with or without impaired intellectual development (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.81
DANN	Benign	0.74
PhyloP100		-0.78
PromoterAI		0.0098	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs1734879; hg19: chr7-101740610; COSMIC: COSV52900143; COSMIC: COSV52900143;