rs12469063

Variant names:

• chr2-66537176-A-G
• rs12469063
• NM_002398.3:c.889-10767A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002398.3(MEIS1):​c.889-10767A>G variant causes a intron change. The variant allele was found at a frequency of 0.185 in 152,174 control chromosomes in the GnomAD database, including 3,213 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 0.19 (3213 hom., cov: 32)
• Consequence: MEIS1 NM_002398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.19
• Publications: 31 publications found

Genes affected

MEIS1 (HGNC:7000): (Meis homeobox 1) Homeobox genes, of which the most well-characterized category is represented by the HOX genes, play a crucial role in normal development. In addition, several homeoproteins are involved in neoplasia. This gene encodes a homeobox protein belonging to the TALE ('three amino acid loop extension') family of homeodomain-containing proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEIS1	NM_002398.3	c.889-10767A>G		intron_variant	Intron 8 of 12	ENST00000272369.14	NP_002389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEIS1	ENST00000272369.14	c.889-10767A>G		intron_variant	Intron 8 of 12	1	NM_002398.3	ENSP00000272369.8

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28237 AN: 152056 Hom.: 3215 Cov.: 32

Gnomad AFR AF: 0.0494

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.185 AC: 28223 AN: 152174 Hom.: 3213 Cov.: 32 AF XY: 0.187 AC XY: 13946 AN XY: 74390

African (AFR) AF: 0.0493 AC: 2048 AN: 41546

American (AMR) AF: 0.189 AC: 2882 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 811 AN: 3472

East Asian (EAS) AF: 0.277 AC: 1429 AN: 5160

South Asian (SAS) AF: 0.257 AC: 1239 AN: 4826

European-Finnish (FIN) AF: 0.243 AC: 2570 AN: 10572

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16383 AN: 68004

Other (OTH) AF: 0.200 AC: 422 AN: 2108

Alfa AF: 0.224 Hom.: 5015

Bravo AF: 0.177

Asia WGS AF: 0.225 AC: 783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Benign	0.87
PhyloP100		4.2
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs12469063; hg19: chr2-66764308;