chr1-46512825-C-T

Variant names:

• chr1-46512825-C-T
• rs2209172
• NM_172225.2:c.*331C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

DMBX1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172225.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMBX1	NM_172225.2	MANE Select	c.*331C>T		3_prime_UTR	Exon 6 of 6	NP_757379.1
	DMBX1	NM_001387776.1		c.*331C>T		3_prime_UTR	Exon 5 of 5	NP_001374705.1
	DMBX1	NM_147192.4		c.*331C>T		3_prime_UTR	Exon 6 of 6	NP_671725.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMBX1	ENST00000360032.4	TSL:1 MANE Select	c.*331C>T		3_prime_UTR	Exon 6 of 6	ENSP00000353132.3

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

African (AFR) AF: 0.143 AC: 939 AN: 6558

American (AMR) AF: 0.141 AC: 1057 AN: 7498

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 1165 AN: 6426

East Asian (EAS) AF: 0.285 AC: 4092 AN: 14356

South Asian (SAS) AF: 0.247 AC: 1479 AN: 5978

European-Finnish (FIN) AF: 0.229 AC: 2477 AN: 10838

Middle Eastern (MID) AF: 0.172 AC: 152 AN: 886

European-Non Finnish (NFE) AF: 0.197 AC: 21579 AN: 109608

Other (OTH) AF: 0.190 AC: 2190 AN: 11504

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

African (AFR) AF: 0.160 AC: 6642 AN: 41508

American (AMR) AF: 0.152 AC: 2327 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 688 AN: 3468

East Asian (EAS) AF: 0.260 AC: 1348 AN: 5178

South Asian (SAS) AF: 0.264 AC: 1270 AN: 4812

European-Finnish (FIN) AF: 0.255 AC: 2707 AN: 10600

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14015 AN: 67998

Other (OTH) AF: 0.180 AC: 381 AN: 2116

Alfa AF: 0.200 Hom.: 9761

Bravo AF: 0.184

Asia WGS AF: 0.217 AC: 753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.5
DANN	Benign	0.79
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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