5-119059022-G-A

Variant names:

• chr5-119059022-G-A
• rs11740134
• ENST00000504820.2:n.97+11784C>T

Variant summary

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

The ENST00000504820.2(DMXL1-DT):​n.97+11784C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,150 control chromosomes in the GnomAD database, including 2,908 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 0.18 (2908 hom., cov: 32)
• Consequence: DMXL1-DT ENST00000504820.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.561
• Publications: 1 publications found

Genes affected

DMXL1-DT (HGNC:55568): (DMXL1 divergent transcript)

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMXL1-DT	NR_134250.1	n.85+11784C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMXL1-DT	ENST00000504820.2	n.97+11784C>T		intron_variant	Intron 1 of 2	4
DMXL1	ENST00000509902.5	n.226+14044G>A		intron_variant	Intron 2 of 4	3
DMXL1-DT	ENST00000510128.2	n.255+11784C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26707 AN: 152032 Hom.: 2907 Cov.: 32

Gnomad AFR AF: 0.0544

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.175 AC: 26697 AN: 152150 Hom.: 2908 Cov.: 32 AF XY: 0.182 AC XY: 13502 AN XY: 74352

African (AFR) AF: 0.0543 AC: 2255 AN: 41554

American (AMR) AF: 0.156 AC: 2378 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 354 AN: 3472

East Asian (EAS) AF: 0.321 AC: 1664 AN: 5182

South Asian (SAS) AF: 0.334 AC: 1612 AN: 4828

European-Finnish (FIN) AF: 0.275 AC: 2903 AN: 10542

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14799 AN: 67996

Other (OTH) AF: 0.148 AC: 313 AN: 2114

Alfa AF: 0.195 Hom.: 5124

Bravo AF: 0.158

Asia WGS AF: 0.295 AC: 1024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.30
DANN	Benign	0.39
PhyloP100		-0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11740134; hg19: chr5-118394717;