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GeneBe

6-31810752-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_005527.4(HSPA1L):c.1221G>A(p.Thr407=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0844 in 1,613,840 control chromosomes in the GnomAD database, including 7,793 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.13 ( 1599 hom., cov: 32)
Exomes 𝑓: 0.080 ( 6194 hom. )

Consequence

HSPA1L
NM_005527.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -9.35
Variant links:
Genes affected
HSPA1L (HGNC:5234): (heat shock protein family A (Hsp70) member 1 like) This gene encodes a 70kDa heat shock protein. In conjunction with other heat shock proteins, this protein stabilizes existing proteins against aggregation and mediates the folding of newly translated proteins in the cytosol and in organelles. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which also encode isoforms of the 70kDa heat shock protein. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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=-0.91).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-31810752-C-T is Benign according to our data. Variant chr6-31810752-C-T is described in ClinVar as [Benign]. Clinvar id is 3059212.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=-9.35 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HSPA1LNM_005527.4 linkuse as main transcriptc.1221G>A p.Thr407= synonymous_variant 2/2 ENST00000375654.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HSPA1LENST00000375654.5 linkuse as main transcriptc.1221G>A p.Thr407= synonymous_variant 2/21 NM_005527.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.126
AC:
19142
AN:
151848
Hom.:
1592
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.214
Gnomad AMI
AF:
0.0208
Gnomad AMR
AF:
0.141
Gnomad ASJ
AF:
0.223
Gnomad EAS
AF:
0.177
Gnomad SAS
AF:
0.0955
Gnomad FIN
AF:
0.0422
Gnomad MID
AF:
0.171
Gnomad NFE
AF:
0.0757
Gnomad OTH
AF:
0.157
GnomAD3 exomes
AF:
0.103
AC:
25959
AN:
251410
Hom.:
1898
AF XY:
0.0982
AC XY:
13342
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.218
Gnomad AMR exome
AF:
0.125
Gnomad ASJ exome
AF:
0.224
Gnomad EAS exome
AF:
0.180
Gnomad SAS exome
AF:
0.0794
Gnomad FIN exome
AF:
0.0408
Gnomad NFE exome
AF:
0.0744
Gnomad OTH exome
AF:
0.123
GnomAD4 exome
AF:
0.0800
AC:
116982
AN:
1461874
Hom.:
6194
Cov.:
37
AF XY:
0.0798
AC XY:
58070
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.218
Gnomad4 AMR exome
AF:
0.130
Gnomad4 ASJ exome
AF:
0.226
Gnomad4 EAS exome
AF:
0.155
Gnomad4 SAS exome
AF:
0.0821
Gnomad4 FIN exome
AF:
0.0408
Gnomad4 NFE exome
AF:
0.0680
Gnomad4 OTH exome
AF:
0.101
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.126
AC:
19164
AN:
151966
Hom.:
1599
Cov.:
32
AF XY:
0.125
AC XY:
9286
AN XY:
74254
show subpopulations
Gnomad4 AFR
AF:
0.214
Gnomad4 AMR
AF:
0.141
Gnomad4 ASJ
AF:
0.223
Gnomad4 EAS
AF:
0.176
Gnomad4 SAS
AF:
0.0956
Gnomad4 FIN
AF:
0.0422
Gnomad4 NFE
AF:
0.0757
Gnomad4 OTH
AF:
0.156
Alfa
AF:
0.0988
Hom.:
1779
Bravo
AF:
0.141
Asia WGS
AF:
0.119
AC:
414
AN:
3478
EpiCase
AF:
0.0883
EpiControl
AF:
0.0908

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

HSPA1L-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 21, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
Cadd
Benign
0.019
Dann
Benign
0.48

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: rs2075799; hg19: chr6-31778529; COSMIC: COSV65149011; COSMIC: COSV65149011; API