NM_003483.6:c.249+40383A>G

Variant names:

• chr12-65878952-A-G
• rs7973574
• NM_003483.6:c.249+40383A>G

Variant summary

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

The NM_003483.6(HMGA2):​c.249+40383A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0729 in 152,230 control chromosomes in the GnomAD database, including 785 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 0.073 (785 hom., cov: 32)
• Consequence: HMGA2 NM_003483.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87
• Publications: 8 publications found

Genes affected

HMGA2 (HGNC:5009): (high mobility group AT-hook 2) This gene encodes a protein that belongs to the non-histone chromosomal high mobility group (HMG) protein family. HMG proteins function as architectural factors and are essential components of the enhancesome. This protein contains structural DNA-binding domains and may act as a transcriptional regulating factor. Identification of the deletion, amplification, and rearrangement of this gene that are associated with myxoid liposarcoma suggests a role in adipogenesis and mesenchymal differentiation. A gene knock out study of the mouse counterpart demonstrated that this gene is involved in diet-induced obesity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

HMGA2-AS1 (HGNC:53973): (HMGA2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGA2	NM_003483.6	c.249+40383A>G		intron_variant	Intron 3 of 4	ENST00000403681.7	NP_003474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMGA2	ENST00000403681.7	c.249+40383A>G		intron_variant	Intron 3 of 4	1	NM_003483.6	ENSP00000384026.2

Frequencies

GnomAD3 genomes AF: 0.0727 AC: 11052 AN: 152112 Hom.: 774 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0463

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.0391

Gnomad SAS AF: 0.0286

Gnomad FIN AF: 0.0322

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0263

Gnomad OTH AF: 0.0659

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

GnomAD4 genome AF: 0.0729 AC: 11093 AN: 152230 Hom.: 785 Cov.: 32 AF XY: 0.0705 AC XY: 5244 AN XY: 74430

African (AFR) AF: 0.186 AC: 7703 AN: 41492

American (AMR) AF: 0.0462 AC: 707 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 38 AN: 3470

East Asian (EAS) AF: 0.0396 AC: 205 AN: 5178

South Asian (SAS) AF: 0.0286 AC: 138 AN: 4826

European-Finnish (FIN) AF: 0.0322 AC: 342 AN: 10614

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0263 AC: 1788 AN: 68032

Other (OTH) AF: 0.0747 AC: 158 AN: 2116

Alfa AF: 0.0411 Hom.: 1087

Bravo AF: 0.0773

Asia WGS AF: 0.0710 AC: 246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.0030
DANN	Benign	0.52
PhyloP100		-1.9
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: rs7973574; hg19: chr12-66272732;