rs7276141

Variant names:

• chr21-28809450-G-C
• rs7276141
• ENST00000824773.1:n.100+12455C>G

Your query was ambiguous. Multiple possible variants found:

• chr21-28809450-G-C
• chr21-28809450-G-T

Variant summary

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

The ENST00000824773.1(ENSG00000232855):​n.100+12455C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0854 in 152,142 control chromosomes in the GnomAD database, including 1,305 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 0.085 (1305 hom., cov: 32)
• Consequence: ENSG00000232855 ENST00000824773.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830
• Publications: 1 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 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.100+12455C>G		intron	N/A
	ENSG00000232855	ENST00000824774.1		n.119+12455C>G		intron	N/A
	ENSG00000232855	ENST00000824775.1		n.104+12455C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0852 AC: 12959 AN: 152024 Hom.: 1301 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0938

Gnomad ASJ AF: 0.0462

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00512

Gnomad OTH AF: 0.0593

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

GnomAD4 genome AF: 0.0854 AC: 12986 AN: 152142 Hom.: 1305 Cov.: 32 AF XY: 0.0867 AC XY: 6447 AN XY: 74398

African (AFR) AF: 0.233 AC: 9685 AN: 41482

American (AMR) AF: 0.0940 AC: 1436 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0462 AC: 160 AN: 3466

East Asian (EAS) AF: 0.136 AC: 706 AN: 5182

South Asian (SAS) AF: 0.0408 AC: 197 AN: 4828

European-Finnish (FIN) AF: 0.0298 AC: 316 AN: 10608

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00512 AC: 348 AN: 67980

Other (OTH) AF: 0.0611 AC: 129 AN: 2112

Alfa AF: 0.00723 Hom.: 5

Bravo AF: 0.0979

Asia WGS AF: 0.0990 AC: 343 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.24
DANN	Benign	0.39
PhyloP100		0.083

Splicing

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

Other links and lift over

dbSNP: rs7276141; hg19: chr21-30181773;