rs17730989

chr2-197497800-C-T

Variant summary

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

The NM_002156.5(HSPD1):c.175-408G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,064 control chromosomes in the GnomAD database, including 13,971 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 0.42 (13971 hom., cov: 33)
• Consequence: HSPD1 NM_002156.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPD1	NM_002156.5	c.175-408G>A		intron_variant		ENST00000388968.8
HSPD1	NM_199440.2	c.175-408G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPD1	ENST00000388968.8	c.175-408G>A		intron_variant		1	NM_002156.5	P1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63821 AN: 151946 Hom.: 13980 Cov.: 33

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.420 AC: 63809 AN: 152064 Hom.: 13971 Cov.: 33 AF XY: 0.418 AC XY: 31078 AN XY: 74310

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.434

Alfa AF: 0.475 Hom.: 16936

Bravo AF: 0.410

Asia WGS AF: 0.391 AC: 1364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.2
Dann	Benign	0.41

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: rs17730989; hg19: chr2-198362524;