chr21-28785829-C-T

Variant names:

• chr21-28785829-C-T
• rs16983288
• ENST00000824773.1:n.100+36076G>A

Variant summary

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

The ENST00000824773.1(LINC03138):​n.100+36076G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,194 control chromosomes in the GnomAD database, including 3,004 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 0.15 (3004 hom., cov: 32)
• Consequence: LINC03138 ENST00000824773.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.757
• Publications: 1 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.348 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

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	ENST00000824773.1		n.100+36076G>A		intron	N/A
	LINC03138	ENST00000824774.1		n.119+36076G>A		intron	N/A
	LINC03138	ENST00000824775.1		n.104+36076G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22027 AN: 152076 Hom.: 2995 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0832

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.0864

Gnomad FIN AF: 0.0707

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0417

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.145 AC: 22075 AN: 152194 Hom.: 3004 Cov.: 32 AF XY: 0.145 AC XY: 10798 AN XY: 74394

African (AFR) AF: 0.353 AC: 14646 AN: 41470

American (AMR) AF: 0.134 AC: 2046 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0832 AC: 289 AN: 3472

East Asian (EAS) AF: 0.147 AC: 762 AN: 5188

South Asian (SAS) AF: 0.0865 AC: 416 AN: 4812

European-Finnish (FIN) AF: 0.0707 AC: 750 AN: 10602

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0417 AC: 2837 AN: 68040

Other (OTH) AF: 0.107 AC: 227 AN: 2112

Alfa AF: 0.0545 Hom.: 138

Bravo AF: 0.159

Asia WGS AF: 0.122 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.62
PhyloP100		-0.76

Splicing

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

Other links and lift over

dbSNP: rs16983288; hg19: chr21-30158151; COSMIC: COSV65802121;