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GeneBe

7-102104343-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_181552.4(CUX1):c.414G>A(p.Thr138=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000618 in 1,604,400 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0031 ( 4 hom., cov: 31)
Exomes 𝑓: 0.00036 ( 5 hom. )

Consequence

CUX1
NM_181552.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.56
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.26).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-102104343-G-A is Benign according to our data. Variant chr7-102104343-G-A is described in ClinVar as [Benign]. Clinvar id is 715004.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.56 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0031 (469/151280) while in subpopulation AFR AF= 0.0107 (442/41178). AF 95% confidence interval is 0.00991. There are 4 homozygotes in gnomad4. There are 222 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 469 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CUX1NM_181552.4 linkuse as main transcriptc.414G>A p.Thr138= synonymous_variant 6/24 ENST00000292535.12
CUX1NM_001913.5 linkuse as main transcriptc.447G>A p.Thr149= synonymous_variant 6/23 ENST00000622516.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CUX1ENST00000292535.12 linkuse as main transcriptc.414G>A p.Thr138= synonymous_variant 6/241 NM_181552.4 A2P39880-1
CUX1ENST00000622516.6 linkuse as main transcriptc.447G>A p.Thr149= synonymous_variant 6/231 NM_001913.5 Q13948-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00310
AC:
469
AN:
151168
Hom.:
4
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0108
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00112
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000883
Gnomad OTH
AF:
0.00192
GnomAD3 exomes
AF:
0.000836
AC:
205
AN:
245210
Hom.:
0
AF XY:
0.000654
AC XY:
87
AN XY:
132950
show subpopulations
Gnomad AFR exome
AF:
0.0112
Gnomad AMR exome
AF:
0.000348
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.0000601
Gnomad NFE exome
AF:
0.0000530
Gnomad OTH exome
AF:
0.000657
GnomAD4 exome
AF:
0.000359
AC:
522
AN:
1453120
Hom.:
5
Cov.:
33
AF XY:
0.000304
AC XY:
220
AN XY:
723140
show subpopulations
Gnomad4 AFR exome
AF:
0.0120
Gnomad4 AMR exome
AF:
0.000427
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000505
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.0000210
Gnomad4 NFE exome
AF:
0.0000441
Gnomad4 OTH exome
AF:
0.000781
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00310
AC:
469
AN:
151280
Hom.:
4
Cov.:
31
AF XY:
0.00301
AC XY:
222
AN XY:
73810
show subpopulations
Gnomad4 AFR
AF:
0.0107
Gnomad4 AMR
AF:
0.00112
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000883
Gnomad4 OTH
AF:
0.00190
Alfa
AF:
0.00170
Hom.:
1
Bravo
AF:
0.00337
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.26
Cadd
Benign
12
Dann
Benign
0.69

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs143157780; hg19: chr7-101747623; API