rs1000756

chr2-66567702-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEIS1	NM_002398.3	c.1024+191G>A		intron_variant		ENST00000272369.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEIS1	ENST00000272369.14	c.1024+191G>A		intron_variant		1	NM_002398.3	P2

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

Gnomad4 AFR exome AF: 0.224

Gnomad4 AMR exome AF: 0.308

Gnomad4 ASJ exome AF: 0.244

Gnomad4 EAS exome AF: 0.177

Gnomad4 SAS exome AF: 0.179

Gnomad4 FIN exome AF: 0.412

Gnomad4 NFE exome AF: 0.355

Gnomad4 OTH exome AF: 0.310

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

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.295

Alfa AF: 0.327 Hom.: 4833

Bravo AF: 0.295

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	16
Dann	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs1000756; hg19: chr2-66794834;