rs7973574

chr12-65878952-A-Gchr12-65878952-A-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
HMGA2	NM_003483.6	c.249+40383A>G		intron_variant		ENST00000403681.7
HMGA2-AS1	NR_158985.1	n.608+2766T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGA2	ENST00000403681.7	c.249+40383A>G		intron_variant		1	NM_003483.6	P1
HMGA2-AS1	ENST00000439236.6	n.450+2766T>C		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.0462

Gnomad4 ASJ AF: 0.0110

Gnomad4 EAS AF: 0.0396

Gnomad4 SAS AF: 0.0286

Gnomad4 FIN AF: 0.0322

Gnomad4 NFE AF: 0.0263

Gnomad4 OTH AF: 0.0747

Alfa AF: 0.0321 Hom.: 273

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

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: rs7973574; hg19: chr12-66272732;