21-28827228-G-C

Variant names:

• chr21-28827228-G-C
• rs1006903
• ENST00000824773.1:n.32-5255C>G

Variant summary

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

The ENST00000824773.1(ENSG00000232855):​n.32-5255C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,050 control chromosomes in the GnomAD database, including 5,879 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 0.23 (5879 hom., cov: 32)
• Consequence: ENSG00000232855 ENST00000824773.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950
• Publications: 4 publications found

Genes affected

ENSG00000232855 (HGNC:58104):

HEMK2 (HGNC:16021): (N-6 adenine-specific DNA methyltransferase 1) This gene encodes an N(6)-adenine-specific DNA methyltransferase. The encoded enzyme may be involved in the methylation of release factor I during translation termination. This enzyme is also involved in converting the arsenic metabolite monomethylarsonous acid to the less toxic dimethylarsonic acid. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 11. [provided by RefSeq, Mar 2023]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000824773.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000232855	ENST00000824773.1		n.32-5255C>G		intron	N/A
	ENSG00000232855	ENST00000824774.1		n.51-5255C>G		intron	N/A
	ENSG00000232855	ENST00000824775.1		n.36-5255C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35556 AN: 151932 Hom.: 5858 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0994

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.234 AC: 35630 AN: 152050 Hom.: 5879 Cov.: 32 AF XY: 0.231 AC XY: 17148 AN XY: 74330

African (AFR) AF: 0.459 AC: 19025 AN: 41430

American (AMR) AF: 0.218 AC: 3331 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 700 AN: 3468

East Asian (EAS) AF: 0.309 AC: 1602 AN: 5178

South Asian (SAS) AF: 0.117 AC: 562 AN: 4822

European-Finnish (FIN) AF: 0.0994 AC: 1053 AN: 10592

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8782 AN: 67982

Other (OTH) AF: 0.218 AC: 459 AN: 2104

Alfa AF: 0.0675 Hom.: 72

Bravo AF: 0.255

Asia WGS AF: 0.225 AC: 783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.8
DANN	Benign	0.36
PhyloP100		0.095

Splicing

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

Other links and lift over

dbSNP: rs1006903; hg19: chr21-30199550;