6-34244966-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000478214.1(HMGA1):​n.531A>T 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 0.0 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0 (0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.012).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGA1	NM_145899.3	c.*82A>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000311487.9	NP_665906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMGA1	ENST00000311487.9	c.*82A>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_145899.3	ENSP00000308227.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 146064 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1351672 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 667810

African (AFR) AF: 0.00 AC: 0 AN: 30572

American (AMR) AF: 0.00 AC: 0 AN: 34884

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24598

East Asian (EAS) AF: 0.00 AC: 0 AN: 35072

South Asian (SAS) AF: 0.00 AC: 0 AN: 78108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4180

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1040768

Other (OTH) AF: 0.00 AC: 0 AN: 55966

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 146064 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 70950

African (AFR) AF: 0.00 AC: 0 AN: 39042

American (AMR) AF: 0.00 AC: 0 AN: 14674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3436

East Asian (EAS) AF: 0.00 AC: 0 AN: 4808

South Asian (SAS) AF: 0.00 AC: 0 AN: 4588

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9732

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66592

Other (OTH) AF: 0.00 AC: 0 AN: 2002

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.11
DANN	Benign	0.93
PhyloP100		-1.7
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

Other links and lift over

dbSNP: rs2780219; hg19: chr6-34212743;