chr2-197489690-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002156.5(HSPD1):​c.970-443A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 151,890 control chromosomes in the GnomAD database, including 38,991 homozygotes. 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 0.71 ( 38991 hom., cov: 30)

Consequence

HSPD1
NM_002156.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.73

Publications

10 publications found
Variant links:
Genes affected
HSPD1 (HGNC:5261): (heat shock protein family D (Hsp60) member 1) This gene encodes a member of the chaperonin family. The encoded mitochondrial protein may function as a signaling molecule in the innate immune system. This protein is essential for the folding and assembly of newly imported proteins in the mitochondria. This gene is adjacent to a related family member and the region between the 2 genes functions as a bidirectional promoter. Several pseudogenes have been associated with this gene. Two transcript variants encoding the same protein have been identified for this gene. Mutations associated with this gene cause autosomal recessive spastic paraplegia 13. [provided by RefSeq, Jun 2010]
HSPD1 Gene-Disease associations (from GenCC):
  • hereditary spastic paraplegia 13
    Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • hypomyelinating leukodystrophy 4
    Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.0).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HSPD1NM_002156.5 linkc.970-443A>G intron_variant Intron 8 of 11 ENST00000388968.8 NP_002147.2 P10809-1A0A024R3X4
HSPD1NM_199440.2 linkc.970-443A>G intron_variant Intron 8 of 11 NP_955472.1 P10809-1A0A024R3X4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HSPD1ENST00000388968.8 linkc.970-443A>G intron_variant Intron 8 of 11 1 NM_002156.5 ENSP00000373620.3 P10809-1

Frequencies

GnomAD3 genomes
AF:
0.709
AC:
107627
AN:
151772
Hom.:
38953
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.845
Gnomad AMI
AF:
0.714
Gnomad AMR
AF:
0.650
Gnomad ASJ
AF:
0.747
Gnomad EAS
AF:
0.507
Gnomad SAS
AF:
0.697
Gnomad FIN
AF:
0.571
Gnomad MID
AF:
0.861
Gnomad NFE
AF:
0.674
Gnomad OTH
AF:
0.728
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.709
AC:
107720
AN:
151890
Hom.:
38991
Cov.:
30
AF XY:
0.705
AC XY:
52313
AN XY:
74220
show subpopulations
African (AFR)
AF:
0.845
AC:
35041
AN:
41448
American (AMR)
AF:
0.649
AC:
9896
AN:
15242
Ashkenazi Jewish (ASJ)
AF:
0.747
AC:
2589
AN:
3464
East Asian (EAS)
AF:
0.508
AC:
2616
AN:
5148
South Asian (SAS)
AF:
0.698
AC:
3354
AN:
4808
European-Finnish (FIN)
AF:
0.571
AC:
6024
AN:
10546
Middle Eastern (MID)
AF:
0.864
AC:
254
AN:
294
European-Non Finnish (NFE)
AF:
0.674
AC:
45763
AN:
67922
Other (OTH)
AF:
0.727
AC:
1532
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1512
3025
4537
6050
7562
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
820
1640
2460
3280
4100
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.696
Hom.:
46669
Bravo
AF:
0.719
Asia WGS
AF:
0.617
AC:
2151
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.93
DANN
Benign
0.16
PhyloP100
-1.7
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs2565163; hg19: chr2-198354414; API