21-28778098-G-T

Variant names:

• chr21-28778098-G-T
• rs8130766
• ENST00000824773.1:n.100+43807C>A

Variant summary

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

The ENST00000824773.1(ENSG00000232855):​n.100+43807C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0815 in 152,150 control chromosomes in the GnomAD database, including 1,163 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 0.081 (1163 hom., cov: 32)
• Consequence: ENSG00000232855 ENST00000824773.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820
• Publications: 3 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=-1.08).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000232855	ENST00000824773.1		n.100+43807C>A		intron	N/A
	ENSG00000232855	ENST00000824774.1		n.119+43807C>A		intron	N/A
	ENSG00000232855	ENST00000824775.1		n.104+43807C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0814 AC: 12370 AN: 152032 Hom.: 1162 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0929

Gnomad ASJ AF: 0.0461

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.0398

Gnomad FIN AF: 0.0364

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00532

Gnomad OTH AF: 0.0589

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

GnomAD4 genome AF: 0.0815 AC: 12393 AN: 152150 Hom.: 1163 Cov.: 32 AF XY: 0.0828 AC XY: 6158 AN XY: 74378

African (AFR) AF: 0.216 AC: 8980 AN: 41496

American (AMR) AF: 0.0931 AC: 1423 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0461 AC: 160 AN: 3468

East Asian (EAS) AF: 0.146 AC: 754 AN: 5158

South Asian (SAS) AF: 0.0396 AC: 191 AN: 4820

European-Finnish (FIN) AF: 0.0364 AC: 386 AN: 10596

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00532 AC: 362 AN: 68006

Other (OTH) AF: 0.0601 AC: 127 AN: 2112

Alfa AF: 0.0439 Hom.: 165

Bravo AF: 0.0928

Asia WGS AF: 0.0990 AC: 345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.47
DANN	Benign	0.17
PhyloP100		0.082

Splicing

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

Other links and lift over

dbSNP: rs8130766; hg19: chr21-30150420;