rs4075

chr4-4862299-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002448.3(MSX1):c.470-402G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 367,588 control chromosomes in the GnomAD database, including 17,996 homozygotes. 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: 𝑓 0.30 (7687 hom., cov: 34)
  • Exomes 𝑓: 0.29 (10309 hom.)
• Consequence: MSX1 NM_002448.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.445

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSX1	NM_002448.3	c.470-402G>T		intron_variant		ENST00000382723.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSX1	ENST00000382723.5	c.470-402G>T		intron_variant		1	NM_002448.3	P1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46071 AN: 152066 Hom.: 7673 Cov.: 34

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.289

GnomAD4 exome AF: 0.294 AC: 63327 AN: 215404 Hom.: 10309 AF XY: 0.291 AC XY: 33829 AN XY: 116118

Gnomad4 AFR exome AF: 0.244

Gnomad4 AMR exome AF: 0.464

Gnomad4 ASJ exome AF: 0.206

Gnomad4 EAS exome AF: 0.598

Gnomad4 SAS exome AF: 0.259

Gnomad4 FIN exome AF: 0.370

Gnomad4 NFE exome AF: 0.271

Gnomad4 OTH exome AF: 0.287

GnomAD4 genome AF: 0.303 AC: 46122 AN: 152184 Hom.: 7687 Cov.: 34 AF XY: 0.312 AC XY: 23227 AN XY: 74400

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.295

Alfa AF: 0.283 Hom.: 1267

Bravo AF: 0.305

Asia WGS AF: 0.409 AC: 1420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	6.0
Dann	Benign	0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs4075; hg19: chr4-4864026; COSMIC: COSV66947278; COSMIC: COSV66947278;