chr2-66533179-A-G

Variant names:

• chr2-66533179-A-G
• rs4433986
• NM_002398.3:c.889-14764A>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.889-14764A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 151,948 control chromosomes in the GnomAD database, including 27,855 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 0.60 (27855 hom., cov: 31)
• Consequence: MEIS1 NM_002398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.04
• Publications: 2 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=-0.29).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002398.3. 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
	MEIS1	NM_002398.3	MANE Select	c.889-14764A>G		intron	N/A	NP_002389.1	O00470-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEIS1	ENST00000272369.14	TSL:1 MANE Select	c.889-14764A>G		intron	N/A	ENSP00000272369.8	O00470-1
	MEIS1	ENST00000488550.5	TSL:1	c.889-14764A>G		intron	N/A	ENSP00000475161.1	U3KPR8
	MEIS1	ENST00000398506.6	TSL:5	c.883-14764A>G		intron	N/A	ENSP00000381518.2	O00470-2

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91079 AN: 151830 Hom.: 27842 Cov.: 31

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.600 AC: 91124 AN: 151948 Hom.: 27855 Cov.: 31 AF XY: 0.607 AC XY: 45094 AN XY: 74252

African (AFR) AF: 0.512 AC: 21216 AN: 41406

American (AMR) AF: 0.677 AC: 10349 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2375 AN: 3470

East Asian (EAS) AF: 0.810 AC: 4175 AN: 5156

South Asian (SAS) AF: 0.784 AC: 3776 AN: 4818

European-Finnish (FIN) AF: 0.595 AC: 6278 AN: 10552

Middle Eastern (MID) AF: 0.596 AC: 174 AN: 292

European-Non Finnish (NFE) AF: 0.601 AC: 40832 AN: 67960

Other (OTH) AF: 0.634 AC: 1334 AN: 2104

Alfa AF: 0.609 Hom.: 106333

Bravo AF: 0.604

Asia WGS AF: 0.758 AC: 2635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	16
DANN	Benign	0.73
PhyloP100		3.0
Mutation Taster		=100/0	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: rs4433986; hg19: chr2-66760311;