rs1042484

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002448.3(MSX1):​c.470-47A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,597,544 control chromosomes in the GnomAD database, including 40,406 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3176 hom., cov: 34)
Exomes 𝑓: 0.22 ( 37230 hom. )

Consequence

MSX1
NM_002448.3 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.634
Variant links:
Genes affected
MSX1 (HGNC:7391): (msh homeobox 1) This gene encodes a member of the muscle segment homeobox gene family. The encoded protein functions as a transcriptional repressor during embryogenesis through interactions with components of the core transcription complex and other homeoproteins. It may also have roles in limb-pattern formation, craniofacial development, particularly odontogenesis, and tumor growth inhibition. Mutations in this gene, which was once known as homeobox 7, have been associated with nonsyndromic cleft lip with or without cleft palate 5, Witkop syndrome, Wolf-Hirschom syndrome, and autosomoal dominant hypodontia. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 4-4862654-A-G is Benign according to our data. Variant chr4-4862654-A-G is described in ClinVar as [Benign]. Clinvar id is 1241303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MSX1NM_002448.3 linkuse as main transcriptc.470-47A>G intron_variant ENST00000382723.5 NP_002439.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MSX1ENST00000382723.5 linkuse as main transcriptc.470-47A>G intron_variant 1 NM_002448.3 ENSP00000372170 P1
MSX1ENST00000468421.1 linkuse as main transcriptn.181+46A>G intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.198
AC:
30110
AN:
152052
Hom.:
3177
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.141
Gnomad AMI
AF:
0.156
Gnomad AMR
AF:
0.204
Gnomad ASJ
AF:
0.244
Gnomad EAS
AF:
0.0513
Gnomad SAS
AF:
0.151
Gnomad FIN
AF:
0.261
Gnomad MID
AF:
0.280
Gnomad NFE
AF:
0.234
Gnomad OTH
AF:
0.202
GnomAD3 exomes
AF:
0.204
AC:
48045
AN:
235490
Hom.:
5239
AF XY:
0.203
AC XY:
26321
AN XY:
129794
show subpopulations
Gnomad AFR exome
AF:
0.145
Gnomad AMR exome
AF:
0.215
Gnomad ASJ exome
AF:
0.244
Gnomad EAS exome
AF:
0.0468
Gnomad SAS exome
AF:
0.158
Gnomad FIN exome
AF:
0.251
Gnomad NFE exome
AF:
0.236
Gnomad OTH exome
AF:
0.223
GnomAD4 exome
AF:
0.223
AC:
322526
AN:
1445374
Hom.:
37230
Cov.:
30
AF XY:
0.222
AC XY:
159589
AN XY:
719978
show subpopulations
Gnomad4 AFR exome
AF:
0.139
Gnomad4 AMR exome
AF:
0.212
Gnomad4 ASJ exome
AF:
0.241
Gnomad4 EAS exome
AF:
0.0588
Gnomad4 SAS exome
AF:
0.159
Gnomad4 FIN exome
AF:
0.252
Gnomad4 NFE exome
AF:
0.236
Gnomad4 OTH exome
AF:
0.208
GnomAD4 genome
AF:
0.198
AC:
30118
AN:
152170
Hom.:
3176
Cov.:
34
AF XY:
0.198
AC XY:
14710
AN XY:
74408
show subpopulations
Gnomad4 AFR
AF:
0.142
Gnomad4 AMR
AF:
0.204
Gnomad4 ASJ
AF:
0.244
Gnomad4 EAS
AF:
0.0512
Gnomad4 SAS
AF:
0.150
Gnomad4 FIN
AF:
0.261
Gnomad4 NFE
AF:
0.234
Gnomad4 OTH
AF:
0.200
Alfa
AF:
0.227
Hom.:
4075
Bravo
AF:
0.192
Asia WGS
AF:
0.110
AC:
384
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxMay 13, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
0.073
DANN
Benign
0.47

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs1042484; hg19: chr4-4864381; COSMIC: COSV66947264; API