ENST00000478214.1:n.531A>G

Variant names:

• chr6-34244966-A-G
• rs2780219
• ENST00000478214.1:n.531A>G

Variant summary

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

The ENST00000478214.1(HMGA1):​n.531A>G variant causes a non coding transcript exon 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 ENST00000478214.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 12 publications found

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]

HMGA1 Gene-Disease associations (from GenCC):

• type 2 diabetes mellitus

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (REVEL=0.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.989 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000478214.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGA1	NM_145899.3	MANE Select	c.*82A>G		3_prime_UTR	Exon 6 of 6	NP_665906.1
	HMGA1	NM_001319078.2		c.*82A>G		3_prime_UTR	Exon 5 of 5	NP_001306007.1
	HMGA1	NM_001319079.2		c.*82A>G		3_prime_UTR	Exon 6 of 6	NP_001306008.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGA1	ENST00000478214.1	TSL:1	n.531A>G		non_coding_transcript_exon	Exon 5 of 5
	HMGA1	ENST00000311487.9	TSL:1 MANE Select	c.*82A>G		3_prime_UTR	Exon 6 of 6	ENSP00000308227.4
	HMGA1	ENST00000447654.5	TSL:1	c.*82A>G		3_prime_UTR	Exon 5 of 5	ENSP00000399888.1

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

GnomAD2 exomes AF: 0.991 AC: 147470 AN: 148880 AF XY: 0.992

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 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

African (AFR) AF: 0.928 AC: 28360 AN: 30566

American (AMR) AF: 0.968 AC: 33769 AN: 34882

Ashkenazi Jewish (ASJ) AF: 0.968 AC: 23818 AN: 24594

East Asian (EAS) AF: 0.994 AC: 34862 AN: 35072

South Asian (SAS) AF: 0.996 AC: 77761 AN: 78108

European-Finnish (FIN) AF: 0.998 AC: 47441 AN: 47524

Middle Eastern (MID) AF: 0.978 AC: 4088 AN: 4178

European-Non Finnish (NFE) AF: 0.987 AC: 1027223 AN: 1040760

Other (OTH) AF: 0.982 AC: 54959 AN: 55960

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

African (AFR) AF: 0.938 AC: 36713 AN: 39140

American (AMR) AF: 0.980 AC: 14402 AN: 14694

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 3349 AN: 3436

East Asian (EAS) AF: 0.996 AC: 4781 AN: 4800

South Asian (SAS) AF: 0.995 AC: 4566 AN: 4590

European-Finnish (FIN) AF: 0.995 AC: 9686 AN: 9732

Middle Eastern (MID) AF: 0.986 AC: 282 AN: 286

European-Non Finnish (NFE) AF: 0.995 AC: 66272 AN: 66584

Other (OTH) AF: 0.974 AC: 1971 AN: 2024

Alfa AF: 0.984 Hom.: 7571

Bravo AF: 0.976

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.13
DANN	Benign	0.89
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		3.2
Mutation Taster		=99/1	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: rs2780219; hg19: chr6-34212743; COSMIC: COSV58988178; COSMIC: COSV58988178;