19-45785448-A-T

Variant names:

• chr19-45785448-A-T
• rs3760843
• NM_004943.2:c.1902+146T>A

Variant summary

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

The ENST00000270223.7(DMWD):​c.1902+146T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 1,385,458 control chromosomes in the GnomAD database, including 484,247 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 0.86 (57040 hom., cov: 31)
  • Exomes 𝑓: 0.83 (427207 hom.)
• Consequence: DMWD ENST00000270223.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.887
• Publications: 15 publications found

Genes affected

DMWD (HGNC:2936): (DM1 locus, WD repeat containing) Predicted to be located in dendrite; nucleus; and perikaryon. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000268434 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000270223.7. 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
	DMWD	NM_004943.2	MANE Select	c.1902+146T>A		intron	N/A	NP_004934.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMWD	ENST00000270223.7	TSL:1 MANE Select	c.1902+146T>A		intron	N/A	ENSP00000270223.5
	ENSG00000268434	ENST00000595946.1	TSL:2	c.120+146T>A		intron	N/A	ENSP00000469741.1
	DMWD	ENST00000537879.1	TSL:1	c.66+146T>A		intron	N/A	ENSP00000444820.1

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131292 AN: 152006 Hom.: 56987 Cov.: 31

Gnomad AFR AF: 0.948

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.805

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.845

GnomAD2 exomes AF: 0.857 AC: 28518 AN: 33294 AF XY: 0.854

Gnomad AFR exome AF: 0.946

Gnomad AMR exome AF: 0.877

Gnomad ASJ exome AF: 0.780

Gnomad EAS exome AF: 0.918

Gnomad FIN exome AF: 0.769

Gnomad NFE exome AF: 0.820

Gnomad OTH exome AF: 0.831

GnomAD4 exome AF: 0.832 AC: 1025726 AN: 1233334 Hom.: 427207 Cov.: 61 AF XY: 0.833 AC XY: 494295 AN XY: 593702

African (AFR) AF: 0.952 AC: 24798 AN: 26042

American (AMR) AF: 0.886 AC: 13472 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 14365 AN: 17858

East Asian (EAS) AF: 0.883 AC: 27466 AN: 31096

South Asian (SAS) AF: 0.881 AC: 46197 AN: 52442

European-Finnish (FIN) AF: 0.782 AC: 22893 AN: 29264

Middle Eastern (MID) AF: 0.859 AC: 3011 AN: 3506

European-Non Finnish (NFE) AF: 0.825 AC: 830315 AN: 1006680

Other (OTH) AF: 0.843 AC: 43209 AN: 51238

GnomAD4 genome AF: 0.864 AC: 131407 AN: 152124 Hom.: 57040 Cov.: 31 AF XY: 0.862 AC XY: 64127 AN XY: 74372

African (AFR) AF: 0.948 AC: 39356 AN: 41532

American (AMR) AF: 0.880 AC: 13462 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.805 AC: 2795 AN: 3470

East Asian (EAS) AF: 0.916 AC: 4721 AN: 5154

South Asian (SAS) AF: 0.885 AC: 4267 AN: 4822

European-Finnish (FIN) AF: 0.779 AC: 8242 AN: 10574

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.824 AC: 55977 AN: 67972

Other (OTH) AF: 0.845 AC: 1783 AN: 2110

Alfa AF: 0.840 Hom.: 6307

Bravo AF: 0.874

Asia WGS AF: 0.907 AC: 3155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.51
DANN	Benign	0.43
PhyloP100		-0.89
PromoterAI		0.00040	Neutral
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: rs3760843; hg19: chr19-46288706;