chr6-31810545-G-A
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_005527.4(HSPA1L):c.1428C>T(p.Ile476=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,613,252 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0059 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00072 ( 8 hom. )
Consequence
HSPA1L
NM_005527.4 synonymous
NM_005527.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.77
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
Variant 6-31810545-G-A is Benign according to our data. Variant chr6-31810545-G-A is described in ClinVar as [Benign]. Clinvar id is 789588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.77 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00593 (903/152230) while in subpopulation AFR AF= 0.0195 (809/41492). AF 95% confidence interval is 0.0184. There are 4 homozygotes in gnomad4. There are 420 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 901 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSPA1L | NM_005527.4 | c.1428C>T | p.Ile476= | synonymous_variant | 2/2 | ENST00000375654.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSPA1L | ENST00000375654.5 | c.1428C>T | p.Ile476= | synonymous_variant | 2/2 | 1 | NM_005527.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00592 AC: 901AN: 152112Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.00164 AC: 412AN: 250456Hom.: 3 AF XY: 0.00129 AC XY: 175AN XY: 135346
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GnomAD4 exome AF: 0.000719 AC: 1050AN: 1461022Hom.: 8 Cov.: 36 AF XY: 0.000652 AC XY: 474AN XY: 726786
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
HSPA1L-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 09, 2019 | This 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
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at