Variant 4-4859882-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The NM_002448.3(MSX1):c.-18G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0658 in 1,469,060 control chromosomes in the GnomAD database, including 4,087 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.050 ( 302 hom., cov: 32)

Exomes 𝑓: 0.068 ( 3785 hom. )

Consequence

MSX1
NM_002448.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.549

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]

MSX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 4-4859882-G-A is Benign according to our data. Variant chr4-4859882-G-A is described in ClinVar as [Benign]. Clinvar id is 1231228.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-4859882-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSX1	NM_002448.3 linkuse as main transcript	c.-18G>A		5_prime_UTR_variant	1/2	ENST00000382723.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSX1	ENST00000382723.5 linkuse as main transcript	c.-18G>A		5_prime_UTR_variant	1/2	1	NM_002448.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0503

AC:

7631

AN:

151648

Hom.:

301

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0107

Gnomad AMI

AF:

0.0824

Gnomad AMR

AF:

0.0374

Gnomad ASJ

AF:

0.208

Gnomad EAS

AF:

0.00136

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.0386

Gnomad MID

AF:

0.0801

Gnomad NFE

AF:

0.0690

Gnomad OTH

AF:

0.0610

GnomAD3 exomes

AF:

0.0796

AC:

7369

AN:

92612

Hom.:

472

AF XY:

0.0883

AC XY:

4622

AN XY:

52370

show subpopulations

Gnomad AFR exome

AF:

0.00954

Gnomad AMR exome

AF:

0.0296

Gnomad ASJ exome

AF:

0.216

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.139

Gnomad FIN exome

AF:

0.0466

Gnomad NFE exome

AF:

0.0721

Gnomad OTH exome

AF:

0.0960

GnomAD4 exome

AF:

0.0675

AC:

88968

AN:

1317304

Hom.:

3785

Cov.:

AF XY:

0.0704

AC XY:

45720

AN XY:

649526

show subpopulations

Gnomad4 AFR exome

AF:

0.00875

Gnomad4 AMR exome

AF:

0.0333

Gnomad4 ASJ exome

AF:

0.211

Gnomad4 EAS exome

AF:

0.000141

Gnomad4 SAS exome

AF:

0.134

Gnomad4 FIN exome

AF:

0.0454

Gnomad4 NFE exome

AF:

0.0649

Gnomad4 OTH exome

AF:

0.0705

GnomAD4 genome

AF:

0.0503

AC:

7628

AN:

151756

Hom.:

302

Cov.:

AF XY:

0.0487

AC XY:

3615

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.0107

Gnomad4 AMR

AF:

0.0373

Gnomad4 ASJ

AF:

0.208

Gnomad4 EAS

AF:

0.00136

Gnomad4 SAS

AF:

0.121

Gnomad4 FIN

AF:

0.0386

Gnomad4 NFE

AF:

0.0689

Gnomad4 OTH

AF:

0.0599

Alfa

AF:

0.0290

Hom.:

Bravo

AF:

0.0473

Asia WGS

AF:

0.0330

AC:

116

AN:

3438

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 submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over