Variant 6-34242693-A-AC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_145899.3(HMGA1):c.136-14dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0376 in 1,537,206 control chromosomes in the GnomAD database, including 2,965 homozygotes. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.054 ( 483 hom., cov: 31)

Exomes 𝑓: 0.036 ( 2482 hom. )

Consequence

HMGA1
NM_145899.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: -0.772

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 6-34242693-A-AC is Benign according to our data. Variant chr6-34242693-A-AC is described in ClinVar as [Benign]. Clinvar id is 1277118.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMGA1	NM_145899.3 linkuse as main transcript	c.136-14dup		intron_variant		ENST00000311487.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGA1	ENST00000311487.9 linkuse as main transcript	c.136-14dup		intron_variant		1	NM_145899.3		P17096-1

Frequencies

GnomAD3 genomes

AF:

0.0539

AC:

8188

AN:

151818

Hom.:

473

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0562

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.185

Gnomad ASJ

AF:

0.0540

Gnomad EAS

AF:

0.100

Gnomad SAS

AF:

0.0334

Gnomad FIN

AF:

0.0156

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0263

Gnomad OTH

AF:

0.0647

GnomAD3 exomes

AF:

0.0774

AC:

13344

AN:

172502

Hom.:

1475

AF XY:

0.0678

AC XY:

6205

AN XY:

91530

show subpopulations

Gnomad AFR exome

AF:

0.0528

Gnomad AMR exome

AF:

0.298

Gnomad ASJ exome

AF:

0.0445

Gnomad EAS exome

AF:

0.0960

Gnomad SAS exome

AF:

0.0346

Gnomad FIN exome

AF:

0.0180

Gnomad NFE exome

AF:

0.0270

Gnomad OTH exome

AF:

0.0625

GnomAD4 exome

AF:

0.0358

AC:

49586

AN:

1385270

Hom.:

2482

Cov.:

AF XY:

0.0352

AC XY:

24167

AN XY:

685858

show subpopulations

Gnomad4 AFR exome

AF:

0.0540

Gnomad4 AMR exome

AF:

0.280

Gnomad4 ASJ exome

AF:

0.0469

Gnomad4 EAS exome

AF:

0.107

Gnomad4 SAS exome

AF:

0.0351

Gnomad4 FIN exome

AF:

0.0178

Gnomad4 NFE exome

AF:

0.0244

Gnomad4 OTH exome

AF:

0.0431

GnomAD4 genome

AF:

0.0540

AC:

8211

AN:

151936

Hom.:

483

Cov.:

AF XY:

0.0552

AC XY:

4097

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.0561

Gnomad4 AMR

AF:

0.186

Gnomad4 ASJ

AF:

0.0540

Gnomad4 EAS

AF:

0.0997

Gnomad4 SAS

AF:

0.0333

Gnomad4 FIN

AF:

0.0156

Gnomad4 NFE

AF:

0.0263

Gnomad4 OTH

AF:

0.0650

Bravo

AF:

0.0704

Asia WGS

AF:

0.0700

AC:

242

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 19, 2019

This variant is associated with the following publications: (PMID: 24148075, 26296198, 23512162, 22411136, 22210315, 21364139) -

Diabetes mellitus type 2, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 02, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BranchPoint Hunter

2.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over