rs1000756

Variant names:

• chr2-66567702-G-A
• rs1000756
• NM_002398.3:c.1024+191G>A

Variant summary

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

The NM_002398.3(MEIS1):​c.1024+191G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 671,742 control chromosomes in the GnomAD database, including 35,153 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 0.31 (7637 hom., cov: 31)
  • Exomes 𝑓: 0.32 (27516 hom.)
• Consequence: MEIS1 NM_002398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.882
• Publications: 6 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.356 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEIS1	NM_002398.3	MANE Select	c.1024+191G>A		intron	N/A	NP_002389.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEIS1	ENST00000272369.14	TSL:1 MANE Select	c.1024+191G>A		intron	N/A	ENSP00000272369.8
	MEIS1	ENST00000488550.5	TSL:1	c.1024+191G>A		intron	N/A	ENSP00000475161.1
	MEIS1	ENST00000560281.6	TSL:5	c.*102G>A		3_prime_UTR	Exon 10 of 10	ENSP00000454209.1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46361 AN: 151480 Hom.: 7626 Cov.: 31

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.297

GnomAD4 exome AF: 0.316 AC: 164406 AN: 520142 Hom.: 27516 Cov.: 5 AF XY: 0.308 AC XY: 86437 AN XY: 280520

African (AFR) AF: 0.224 AC: 3067 AN: 13684

American (AMR) AF: 0.308 AC: 8454 AN: 27484

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 4550 AN: 18656

East Asian (EAS) AF: 0.177 AC: 5627 AN: 31748

South Asian (SAS) AF: 0.179 AC: 10210 AN: 57168

European-Finnish (FIN) AF: 0.412 AC: 13835 AN: 33592

Middle Eastern (MID) AF: 0.362 AC: 1029 AN: 2846

European-Non Finnish (NFE) AF: 0.355 AC: 108643 AN: 305992

Other (OTH) AF: 0.310 AC: 8991 AN: 28972

GnomAD4 genome AF: 0.306 AC: 46376 AN: 151600 Hom.: 7637 Cov.: 31 AF XY: 0.304 AC XY: 22504 AN XY: 74042

African (AFR) AF: 0.223 AC: 9220 AN: 41322

American (AMR) AF: 0.314 AC: 4790 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 814 AN: 3468

East Asian (EAS) AF: 0.183 AC: 944 AN: 5168

South Asian (SAS) AF: 0.174 AC: 832 AN: 4790

European-Finnish (FIN) AF: 0.415 AC: 4337 AN: 10444

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24423 AN: 67868

Other (OTH) AF: 0.295 AC: 618 AN: 2098

Alfa AF: 0.330 Hom.: 16731

Bravo AF: 0.295

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	16
DANN	Benign	0.66
PhyloP100		0.88
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1000756; hg19: chr2-66794834;