chr21-28744041-T-C

Variant names:

• chr21-28744041-T-C
• rs2205413
• ENST00000824757.1:n.57+27953A>G

Variant summary

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

The ENST00000824757.1(LINC03138):​n.57+27953A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 151,634 control chromosomes in the GnomAD database, including 20,917 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 0.51 (20917 hom., cov: 30)
• Consequence: LINC03138 ENST00000824757.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 2 publications found

Genes affected

LINC03138 (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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000824757.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC03138	ENST00000824757.1		n.57+27953A>G		intron	N/A
	LINC03138	ENST00000824758.1		n.147+27953A>G		intron	N/A
	LINC03138	ENST00000824759.1		n.139+27953A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76498 AN: 151516 Hom.: 20877 Cov.: 30

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.505 AC: 76585 AN: 151634 Hom.: 20917 Cov.: 30 AF XY: 0.505 AC XY: 37424 AN XY: 74082

African (AFR) AF: 0.693 AC: 28619 AN: 41292

American (AMR) AF: 0.541 AC: 8236 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1809 AN: 3472

East Asian (EAS) AF: 0.778 AC: 3982 AN: 5120

South Asian (SAS) AF: 0.430 AC: 2061 AN: 4794

European-Finnish (FIN) AF: 0.371 AC: 3903 AN: 10512

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.390 AC: 26497 AN: 67904

Other (OTH) AF: 0.523 AC: 1101 AN: 2106

Alfa AF: 0.459 Hom.: 2146

Bravo AF: 0.527

Asia WGS AF: 0.616 AC: 2141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.79
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs2205413; hg19: chr21-30116363;