rs2340690

Positions:

• chr2-197496162-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002156.5(HSPD1):​c.428-786T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,202 control chromosomes in the GnomAD database, including 2,155 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 0.16 (2155 hom., cov: 32)
• Consequence: HSPD1 NM_002156.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.959

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPD1	NM_002156.5	c.428-786T>C		intron_variant		ENST00000388968.8
HSPD1	NM_199440.2	c.428-786T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPD1	ENST00000388968.8	c.428-786T>C		intron_variant		1	NM_002156.5	P1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24027 AN: 152084 Hom.: 2151 Cov.: 32

Gnomad AFR AF: 0.0756

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.183

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.158 AC: 24045 AN: 152202 Hom.: 2155 Cov.: 32 AF XY: 0.159 AC XY: 11854 AN XY: 74412

Gnomad4 AFR AF: 0.0755

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.185

Alfa AF: 0.191 Hom.: 2485

Bravo AF: 0.159

Asia WGS AF: 0.171 AC: 596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	11
DANN	Benign	0.85

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: rs2340690; hg19: chr2-198360886;