rs2833693

Variant names:

• chr21-32180200-T-C
• rs2833693
• ENST00000411605.6:n.126+64922A>G

Variant summary

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

The ENST00000411605.6(LINC00159):​n.126+64922A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,112 control chromosomes in the GnomAD database, including 6,428 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 0.28 (6428 hom., cov: 32)
• Consequence: LINC00159 ENST00000411605.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730
• Publications: 9 publications found

Genes affected

LINC00159 (HGNC:1285): (long intergenic non-protein coding RNA 159)

MIS18A (HGNC:1286): (MIS18 kinetochore protein A) Enables identical protein binding activity. Predicted to be involved in CENP-A containing chromatin assembly and chromosome segregation. Predicted to act upstream of or within regulation of DNA methylation. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIS18A	XR_002958619.2	n.2770-23698A>G		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINC00159	ENST00000411605.6	n.126+64922A>G		intron_variant	Intron 2 of 4	3
LINC00159	ENST00000414877.1	n.39+17575A>G		intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42783 AN: 151994 Hom.: 6425 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.281 AC: 42797 AN: 152112 Hom.: 6428 Cov.: 32 AF XY: 0.285 AC XY: 21188 AN XY: 74366

African (AFR) AF: 0.190 AC: 7901 AN: 41498

American (AMR) AF: 0.414 AC: 6322 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1185 AN: 3466

East Asian (EAS) AF: 0.421 AC: 2180 AN: 5172

South Asian (SAS) AF: 0.278 AC: 1342 AN: 4824

European-Finnish (FIN) AF: 0.283 AC: 2997 AN: 10586

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19878 AN: 67964

Other (OTH) AF: 0.308 AC: 652 AN: 2114

Alfa AF: 0.300 Hom.: 2576

Bravo AF: 0.292

Asia WGS AF: 0.335 AC: 1164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.0
DANN	Benign	0.61
PhyloP100		0.073

Splicing

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

Other links and lift over

dbSNP: rs2833693; hg19: chr21-33552512;