6-34244966-A-G

Variant summary

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

The NM_145899.3(HMGA1):c.*82A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.98 (69861 hom., cov: 20)
  • Exomes 𝑓: 0.99 (656507 hom.)
  • Failed GnomAD Quality Control
• Consequence: HMGA1 NM_145899.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

Genes affected

HMGA1 (HGNC:5010): (high mobility group AT-hook 1) This gene encodes a chromatin-associated protein involved in the regulation of gene transcription, integration of retroviruses into chromosomes, and the metastatic progression of cancer cells. The encoded protein preferentially binds to the minor groove of AT-rich regions in double-stranded DNA. Multiple transcript variants encoding different isoforms have been found for this gene. Pseudogenes of this gene have been identified on multiple chromosomes. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.989 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMGA1	NM_145899.3	c.*82A>G		3_prime_UTR_variant	6/6	ENST00000311487.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGA1	ENST00000311487.9	c.*82A>G		3_prime_UTR_variant	6/6	1	NM_145899.3

Frequencies

GnomAD3 genomes AF: 0.978 AC: 142788 AN: 146048 Hom.: 69807 Cov.: 20

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.980

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.995

Gnomad FIN AF: 0.995

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.995

Gnomad OTH AF: 0.974

GnomAD3 exomes AF: 0.991 AC: 147470 AN: 148880 Hom.: 73054 AF XY: 0.992 AC XY: 78831 AN XY: 79476

Gnomad AFR exome AF: 0.936

Gnomad AMR exome AF: 0.984

Gnomad ASJ exome AF: 0.974

Gnomad EAS exome AF: 0.999

Gnomad SAS exome AF: 0.999

Gnomad FIN exome AF: 0.999

Gnomad NFE exome AF: 0.996

Gnomad OTH exome AF: 0.987

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.986 AC: 1332281 AN: 1351644 Hom.: 656507 Cov.: 25 AF XY: 0.987 AC XY: 658886 AN XY: 667798

Gnomad4 AFR exome AF: 0.928

Gnomad4 AMR exome AF: 0.968

Gnomad4 ASJ exome AF: 0.968

Gnomad4 EAS exome AF: 0.994

Gnomad4 SAS exome AF: 0.996

Gnomad4 FIN exome AF: 0.998

Gnomad4 NFE exome AF: 0.987

Gnomad4 OTH exome AF: 0.982

GnomAD4 genome AF: 0.978 AC: 142902 AN: 146168 Hom.: 69861 Cov.: 20 AF XY: 0.978 AC XY: 69514 AN XY: 71062

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.980

Gnomad4 ASJ AF: 0.975

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.995

Gnomad4 FIN AF: 0.995

Gnomad4 NFE AF: 0.995

Gnomad4 OTH AF: 0.974

Alfa AF: 0.984 Hom.: 7571

Bravo AF: 0.976

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	0.13
Dann	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		3.2

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: rs2780219; hg19: chr6-34212743; COSMIC: COSV58988178; COSMIC: COSV58988178;