1-44215811-C-G

Position:

• chr1-44215811-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019100.5(DMAP1):​c.393+913C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 163,430 control chromosomes in the GnomAD database, including 40,061 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 0.70 (37919 hom., cov: 32)
  • Exomes 𝑓: 0.62 (2142 hom.)
• Consequence: DMAP1 NM_019100.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214

Genes affected

DMAP1 (HGNC:18291): (DNA methyltransferase 1 associated protein 1) This gene encodes a subunit of several, distinct complexes involved in the repression or activation of transcription. The encoded protein can independently repress transcription and is targeted to replication foci throughout S phase by interacting directly with the N-terminus of DNA methyltransferase 1. During late S phase, histone deacetylase 2 is added to this complex, providing a means to deacetylate histones in transcriptionally inactive heterochromatin following replication. The encoded protein is also a component of the nucleosome acetyltransferase of H4 complex and interacts with the transcriptional corepressor tumor susceptibility gene 101 and the pro-apoptotic death-associated protein 6, among others. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMAP1	NM_019100.5	c.393+913C>G		intron_variant		ENST00000372289.7	NP_061973.1
DMAP1	NM_001034023.2	c.393+913C>G		intron_variant			NP_001029195.1
DMAP1	NM_001034024.2	c.393+913C>G		intron_variant			NP_001029196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMAP1	ENST00000372289.7	c.393+913C>G		intron_variant		1	NM_019100.5	ENSP00000361363	P1

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105846 AN: 152020 Hom.: 37847 Cov.: 32

Gnomad AFR AF: 0.872

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.673

GnomAD4 exome AF: 0.616 AC: 6960 AN: 11292 Hom.: 2142 Cov.: 0 AF XY: 0.613 AC XY: 3677 AN XY: 5994

Gnomad4 AFR exome AF: 0.923

Gnomad4 AMR exome AF: 0.662

Gnomad4 ASJ exome AF: 0.643

Gnomad4 EAS exome AF: 0.446

Gnomad4 SAS exome AF: 0.689

Gnomad4 FIN exome AF: 0.659

Gnomad4 NFE exome AF: 0.593

Gnomad4 OTH exome AF: 0.622

GnomAD4 genome AF: 0.697 AC: 105981 AN: 152138 Hom.: 37919 Cov.: 32 AF XY: 0.699 AC XY: 51976 AN XY: 74378

Gnomad4 AFR AF: 0.872

Gnomad4 AMR AF: 0.690

Gnomad4 ASJ AF: 0.670

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.726

Gnomad4 FIN AF: 0.672

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.676

Alfa AF: 0.656 Hom.: 4167

Bravo AF: 0.704

Asia WGS AF: 0.687 AC: 2389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	7.8
DANN	Benign	0.28

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: rs709267; hg19: chr1-44681483;