chr1-46512825-C-T

Position:

• chr1-46512825-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_172225.2(DMBX1):​c.*331C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 325,822 control chromosomes in the GnomAD database, including 6,929 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 0.20 (2993 hom., cov: 32)
  • Exomes 𝑓: 0.20 (3936 hom.)
• Consequence: DMBX1 NM_172225.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.996

Genes affected

DMBX1 (HGNC:19026): (diencephalon/mesencephalon homeobox 1) This gene encodes a member of the bicoid sub-family of homeodomain-containing transcription factors. The encoded protein acts as a transcription factor and may play a role in brain and sensory organ development. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMBX1	NM_172225.2	c.*331C>T		3_prime_UTR_variant	6/6	ENST00000360032.4
DMBX1	NM_001387775.1	c.*331C>T		3_prime_UTR_variant	5/5
DMBX1	NM_001387776.1	c.*331C>T		3_prime_UTR_variant	5/5
DMBX1	NM_147192.4	c.*331C>T		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMBX1	ENST00000360032.4	c.*331C>T		3_prime_UTR_variant	6/6	1	NM_172225.2	P1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29700 AN: 152052 Hom.: 2993 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.182

GnomAD4 exome AF: 0.202 AC: 35130 AN: 173652 Hom.: 3936 Cov.: 0 AF XY: 0.202 AC XY: 17708 AN XY: 87828

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.141

Gnomad4 ASJ exome AF: 0.181

Gnomad4 EAS exome AF: 0.285

Gnomad4 SAS exome AF: 0.247

Gnomad4 FIN exome AF: 0.229

Gnomad4 NFE exome AF: 0.197

Gnomad4 OTH exome AF: 0.190

GnomAD4 genome AF: 0.195 AC: 29706 AN: 152170 Hom.: 2993 Cov.: 32 AF XY: 0.196 AC XY: 14600 AN XY: 74400

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.180

Alfa AF: 0.204 Hom.: 6605

Bravo AF: 0.184

Asia WGS AF: 0.217 AC: 753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.5
DANN	Benign	0.79

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

Other links and lift over

dbSNP: rs2209172; hg19: chr1-46978497; COSMIC: COSV63602527;