chr2-66544868-T-C

Variant names:

• chr2-66544868-T-C
• rs11897119
• NM_002398.3:c.889-3075T>C

Variant summary

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

The NM_002398.3(MEIS1):​c.889-3075T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,980 control chromosomes in the GnomAD database, including 10,771 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 0.37 (10771 hom., cov: 32)
• Consequence: MEIS1 NM_002398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• Publications: 37 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.396 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.889-3075T>C		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.889-3075T>C		intron	N/A	ENSP00000272369.8	O00470-1
	MEIS1	ENST00000488550.5	TSL:1	c.889-3075T>C		intron	N/A	ENSP00000475161.1	U3KPR8
	MEIS1	ENST00000398506.6	TSL:5	c.883-3075T>C		intron	N/A	ENSP00000381518.2	O00470-2

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56101 AN: 151862 Hom.: 10751 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.370 AC: 56158 AN: 151980 Hom.: 10771 Cov.: 32 AF XY: 0.366 AC XY: 27152 AN XY: 74276

African (AFR) AF: 0.365 AC: 15152 AN: 41456

American (AMR) AF: 0.312 AC: 4758 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1115 AN: 3464

East Asian (EAS) AF: 0.190 AC: 980 AN: 5168

South Asian (SAS) AF: 0.217 AC: 1046 AN: 4828

European-Finnish (FIN) AF: 0.453 AC: 4773 AN: 10532

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27186 AN: 67966

Other (OTH) AF: 0.346 AC: 731 AN: 2110

Alfa AF: 0.379 Hom.: 33342

Bravo AF: 0.357

Asia WGS AF: 0.235 AC: 815 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.67
PhyloP100		-0.0010
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: rs11897119; hg19: chr2-66772000;