Variant chr6-34240837-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_145899.3(HMGA1):c.57C>T(p.Asp19=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00316 in 1,613,250 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0094 ( 18 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 35 hom. )

Consequence

HMGA1
NM_145899.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.400

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 6-34240837-C-T is Benign according to our data. Variant chr6-34240837-C-T is described in ClinVar as [Benign]. Clinvar id is 783751.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.4 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00943 (1436/152250) while in subpopulation AFR AF= 0.026 (1081/41536). AF 95% confidence interval is 0.0247. There are 18 homozygotes in gnomad4. There are 667 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1436 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGA1	NM_145899.3 linkuse as main transcript	c.57C>T	p.Asp19=	synonymous_variant	3/6	ENST00000311487.9	NP_665906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMGA1	ENST00000311487.9 linkuse as main transcript	c.57C>T	p.Asp19=	synonymous_variant	3/6	1	NM_145899.3	ENSP00000308227		P17096-1

Frequencies

GnomAD3 genomes

AF:

0.00943

AC:

1435

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0261

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00642

Gnomad ASJ

AF:

0.0242

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00198

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.00480

AC:

1202

AN:

250454

Hom.:

AF XY:

0.00416

AC XY:

564

AN XY:

135680

show subpopulations

Gnomad AFR exome

AF:

0.0273

Gnomad AMR exome

AF:

0.00688

Gnomad ASJ exome

AF:

0.0242

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.00199

Gnomad OTH exome

AF:

0.00573

GnomAD4 exome

AF:

0.00250

AC:

3655

AN:

1461000

Hom.:

Cov.:

AF XY:

0.00241

AC XY:

1755

AN XY:

726802

show subpopulations

Gnomad4 AFR exome

AF:

0.0252

Gnomad4 AMR exome

AF:

0.00704

Gnomad4 ASJ exome

AF:

0.0244

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000580

Gnomad4 FIN exome

AF:

0.000262

Gnomad4 NFE exome

AF:

0.00131

Gnomad4 OTH exome

AF:

0.00482

GnomAD4 genome

AF:

0.00943

AC:

1436

AN:

152250

Hom.:

Cov.:

AF XY:

0.00896

AC XY:

667

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0260

Gnomad4 AMR

AF:

0.00641

Gnomad4 ASJ

AF:

0.0242

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00198

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00671

Hom.:

Bravo

AF:

0.0106

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00218

EpiControl

AF:

0.00284

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.84

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

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