rs2300478

chr2-66554321-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002398.3(MEIS1):c.965+6302T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,136 control chromosomes in the GnomAD database, including 3,676 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 0.21 (3676 hom., cov: 33)
• Consequence: MEIS1 NM_002398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82

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]

LOC124900511 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEIS1	NM_002398.3	c.965+6302T>G		intron_variant		ENST00000272369.14
LOC124900511	XR_007086610.1	n.6297T>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEIS1	ENST00000272369.14	c.965+6302T>G		intron_variant		1	NM_002398.3	P2

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32352 AN: 152018 Hom.: 3679 Cov.: 33

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.213 AC: 32341 AN: 152136 Hom.: 3676 Cov.: 33 AF XY: 0.214 AC XY: 15929 AN XY: 74358

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.229

Alfa AF: 0.242 Hom.: 9886

Bravo AF: 0.208

Asia WGS AF: 0.229 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	9.4
Dann	Benign	0.31

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

Publications

LitVar

Other links and lift over

dbSNP: rs2300478; hg19: chr2-66781453;