rs4895185

Variant names:

• chr5-119138414-A-G
• rs4895185
• NM_001290321.3:c.2376+4025A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001290321.3(DMXL1):​c.2376+4025A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,156 control chromosomes in the GnomAD database, including 5,342 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 0.24 (5342 hom., cov: 32)
• Consequence: DMXL1 NM_001290321.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342
• Publications: 1 publications found

Genes affected

DMXL1 (HGNC:2937): (Dmx like 1) The protein encoded by this gene is a member of the WD repeat superfamily of proteins, which have regulatory functions. This gene is expressed in many tissue types including several types of eye tissue, and it has been associated with ocular phenotypes. In addition, it is upregulated in cultured cells that overexpress growth factor independence 1B, a transcription factor that is essential for hematopoietic cell development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290321.3. 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
	DMXL1	NM_001290321.3	MANE Select	c.2376+4025A>G		intron	N/A	NP_001277250.1
	DMXL1	NM_001349239.2		c.2376+4025A>G		intron	N/A	NP_001336168.1
	DMXL1	NM_001349240.2		c.2376+4025A>G		intron	N/A	NP_001336169.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMXL1	ENST00000539542.6	TSL:1 MANE Select	c.2376+4025A>G		intron	N/A	ENSP00000439479.1
	DMXL1	ENST00000311085.8	TSL:1	c.2376+4025A>G		intron	N/A	ENSP00000309690.8
	DMXL1	ENST00000512281.1	TSL:3	n.164+4025A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37241 AN: 152038 Hom.: 5342 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.0262

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.284

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.245 AC: 37254 AN: 152156 Hom.: 5342 Cov.: 32 AF XY: 0.237 AC XY: 17648 AN XY: 74388

African (AFR) AF: 0.122 AC: 5084 AN: 41522

American (AMR) AF: 0.221 AC: 3374 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1453 AN: 3470

East Asian (EAS) AF: 0.0264 AC: 137 AN: 5184

South Asian (SAS) AF: 0.221 AC: 1063 AN: 4820

European-Finnish (FIN) AF: 0.223 AC: 2363 AN: 10584

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22940 AN: 67974

Other (OTH) AF: 0.286 AC: 604 AN: 2112

Alfa AF: 0.310 Hom.: 33483

Bravo AF: 0.239

Asia WGS AF: 0.146 AC: 508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.8
DANN	Benign	0.80
PhyloP100		0.34
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: rs4895185; hg19: chr5-118474109;