chr21-28810789-G-T

Variant names:

• chr21-28810789-G-T
• rs7281691
• ENST00000824773.1:n.100+11116C>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+11116C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,046 control chromosomes in the GnomAD database, including 2,352 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 0.11 (2352 hom., cov: 31)
• Consequence: LINC03138 ENST00000824773.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 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+11116C>A		intron	N/A
	LINC03138	ENST00000824774.1		n.119+11116C>A		intron	N/A
	LINC03138	ENST00000824775.1		n.104+11116C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16888 AN: 151928 Hom.: 2345 Cov.: 31

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.0421

Gnomad FIN AF: 0.0296

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00532

Gnomad OTH AF: 0.0774

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

GnomAD4 genome AF: 0.111 AC: 16921 AN: 152046 Hom.: 2352 Cov.: 31 AF XY: 0.111 AC XY: 8282 AN XY: 74340

African (AFR) AF: 0.324 AC: 13405 AN: 41384

American (AMR) AF: 0.103 AC: 1570 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0542 AC: 188 AN: 3470

East Asian (EAS) AF: 0.137 AC: 705 AN: 5164

South Asian (SAS) AF: 0.0413 AC: 199 AN: 4822

European-Finnish (FIN) AF: 0.0296 AC: 314 AN: 10598

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00532 AC: 362 AN: 68004

Other (OTH) AF: 0.0789 AC: 167 AN: 2116

Alfa AF: 0.0550 Hom.: 1949

Bravo AF: 0.127

Asia WGS AF: 0.104 AC: 360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.52
PhyloP100		-0.19

Splicing

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

Other links and lift over

dbSNP: rs7281691; hg19: chr21-30183112;