rs1236428

Variant names:

• chr21-28600947-C-T
• rs1236428
• ENST00000430247.1:n.21-23567G>A

Variant summary

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

The ENST00000433310.6(LINC03138):​n.295-23567G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 152,222 control chromosomes in the GnomAD database, including 55,599 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 0.85 (55599 hom., cov: 32)
• Consequence: LINC03138 ENST00000433310.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176
• Publications: 0 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000433310.6. 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	ENST00000430247.1	TSL:5	n.21-23567G>A		intron	N/A
	LINC03138	ENST00000433310.6	TSL:2	n.295-23567G>A		intron	N/A
	LINC03138	ENST00000824757.1		n.150-23567G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129463 AN: 152104 Hom.: 55536 Cov.: 32

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.883

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.794

Gnomad OTH AF: 0.842

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

GnomAD4 genome AF: 0.851 AC: 129583 AN: 152222 Hom.: 55599 Cov.: 32 AF XY: 0.852 AC XY: 63445 AN XY: 74436

African (AFR) AF: 0.938 AC: 38972 AN: 41550

American (AMR) AF: 0.883 AC: 13506 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.927 AC: 3217 AN: 3470

East Asian (EAS) AF: 0.916 AC: 4743 AN: 5178

South Asian (SAS) AF: 0.837 AC: 4039 AN: 4826

European-Finnish (FIN) AF: 0.778 AC: 8240 AN: 10588

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.794 AC: 54000 AN: 68000

Other (OTH) AF: 0.840 AC: 1774 AN: 2112

Alfa AF: 0.823 Hom.: 28251

Bravo AF: 0.869

Asia WGS AF: 0.844 AC: 2937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.7
DANN	Benign	0.42
PhyloP100		-0.18

Splicing

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

Other links and lift over

dbSNP: rs1236428; hg19: chr21-29973269;