Variant 6-34243461-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_145899.3(HMGA1):c.220-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0382 in 1,610,404 control chromosomes in the GnomAD database, including 1,417 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.027 ( 80 hom., cov: 32)

Exomes 𝑓: 0.039 ( 1337 hom. )

Consequence

HMGA1
NM_145899.3 splice_region, intron

Scores

Splicing: ADA: 0.00005694

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.268

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0273 (4153/152106) while in subpopulation NFE AF= 0.0418 (2841/68014). AF 95% confidence interval is 0.0405. There are 80 homozygotes in gnomad4. There are 1968 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4153 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGA1	NM_145899.3 link	c.220-7C>T		splice_region_variant, intron_variant		ENST00000311487.9	NP_665906.1	P17096-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMGA1	ENST00000311487.9 link	c.220-7C>T		splice_region_variant, intron_variant		1	NM_145899.3	ENSP00000308227.4		P17096-1

Frequencies

GnomAD3 genomes

AF:

0.0273

AC:

4152

AN:

151988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00758

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.0191

Gnomad ASJ

AF:

0.0721

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0130

Gnomad FIN

AF:

0.0260

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0418

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.0283

AC:

7102

AN:

250856

Hom.:

141

AF XY:

0.0282

AC XY:

3821

AN XY:

135622

show subpopulations

Gnomad AFR exome

AF:

0.00723

Gnomad AMR exome

AF:

0.0169

Gnomad ASJ exome

AF:

0.0661

Gnomad EAS exome

AF:

0.000653

Gnomad SAS exome

AF:

0.0171

Gnomad FIN exome

AF:

0.0251

Gnomad NFE exome

AF:

0.0395

Gnomad OTH exome

AF:

0.0294

GnomAD4 exome

AF:

0.0393

AC:

57293

AN:

1458298

Hom.:

1337

Cov.:

AF XY:

0.0383

AC XY:

27799

AN XY:

725654

show subpopulations

Gnomad4 AFR exome

AF:

0.00557

Gnomad4 AMR exome

AF:

0.0169

Gnomad4 ASJ exome

AF:

0.0649

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.0170

Gnomad4 FIN exome

AF:

0.0266

Gnomad4 NFE exome

AF:

0.0446

Gnomad4 OTH exome

AF:

0.0384

GnomAD4 genome

AF:

0.0273

AC:

4153

AN:

152106

Hom.:

Cov.:

AF XY:

0.0265

AC XY:

1968

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00755

Gnomad4 AMR

AF:

0.0190

Gnomad4 ASJ

AF:

0.0721

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0133

Gnomad4 FIN

AF:

0.0260

Gnomad4 NFE

AF:

0.0418

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.0358

Hom.:

Bravo

AF:

0.0254

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.0358

EpiControl

AF:

0.0345

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.3

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000057

dbscSNV1_RF

Benign

0.058

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over