rs7585486

Positions:

• chr2-197494303-G-C
• chr2-197494303-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002156.5(HSPD1):​c.607-53C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 899,428 control chromosomes in the GnomAD database, including 13,129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1841 hom., cov: 32)
  • Exomes 𝑓: 0.17 (11288 hom.)
• Consequence: HSPD1 NM_002156.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.87

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 2-197494303-G-C is Benign according to our data. Variant chr2-197494303-G-C is described in ClinVar as [Benign]. Clinvar id is 671556.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPD1	NM_002156.5	c.607-53C>G		intron_variant		ENST00000388968.8
HSPD1	NM_199440.2	c.607-53C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPD1	ENST00000388968.8	c.607-53C>G		intron_variant		1	NM_002156.5	P1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21174 AN: 151902 Hom.: 1838 Cov.: 32

Gnomad AFR AF: 0.0363

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.0938

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.168 AC: 125482 AN: 747408 Hom.: 11288 Cov.: 10 AF XY: 0.166 AC XY: 66128 AN XY: 399194

Gnomad4 AFR exome AF: 0.0323

Gnomad4 AMR exome AF: 0.186

Gnomad4 ASJ exome AF: 0.230

Gnomad4 EAS exome AF: 0.231

Gnomad4 SAS exome AF: 0.0928

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.174

Gnomad4 OTH exome AF: 0.171

GnomAD4 genome AF: 0.139 AC: 21181 AN: 152020 Hom.: 1841 Cov.: 32 AF XY: 0.141 AC XY: 10481 AN XY: 74300

Gnomad4 AFR AF: 0.0363

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.0955

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.169

Alfa AF: 0.145 Hom.: 220

Bravo AF: 0.140

Asia WGS AF: 0.137 AC: 477 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.055
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs7585486; hg19: chr2-198359027; COSMIC: COSV61444608; COSMIC: COSV61444608;