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GeneBe

6-34240837-C-T

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

2

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.4 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1435 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HMGA1NM_145899.3 linkuse as main transcriptc.57C>T p.Asp19= synonymous_variant 3/6 ENST00000311487.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HMGA1ENST00000311487.9 linkuse as main transcriptc.57C>T p.Asp19= synonymous_variant 3/61 NM_145899.3 P17096-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00943
AC:
1435
AN:
152132
Hom.:
18
Cov.:
32
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.:
18
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.:
35
Cov.:
31
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00943
AC:
1436
AN:
152250
Hom.:
18
Cov.:
32
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.:
5
Bravo
AF:
0.0106
Asia WGS
AF:
0.00173
AC:
6
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 submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.45
Cadd
Benign
13
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.

Other links and lift over

dbSNP: rs11266792; hg19: chr6-34208614; COSMIC: COSV61028850; COSMIC: COSV61028850; API