chr2-197500319-C-G

Variant names:

• chr2-197500319-C-G
• rs1116734
• ENST00000915249.1:c.-118C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000409729.1(HSPE1):​c.-118C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 1,497,840 control chromosomes in the GnomAD database, including 340,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (35878 hom., cov: 33)
  • Exomes 𝑓: 0.67 (305074 hom.)
• Consequence: HSPE1 ENST00000409729.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.160
• Publications: 14 publications found

Genes affected

HSPE1 (HGNC:5269): (heat shock protein family E (Hsp10) member 1) This gene encodes a major heat shock protein which functions as a chaperonin. Its structure consists of a heptameric ring which binds to another heat shock protein in order to form a symmetric, functional heterodimer which enhances protein folding in an ATP-dependent manner. This gene and its co-chaperonin, HSPD1, are arranged in a head-to-head orientation on chromosome 2. Naturally occurring read-through transcription occurs between this locus and the neighboring locus MOBKL3.[provided by RefSeq, Feb 2011]

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]

HSPE1-MOB4 (HGNC:49184): (HSPE1-MOB4 readthrough) This locus represents naturally occurring read-through transcription between the neighboring HSPE1 (heat shock 10kDa protein 1 (chaperonin 10)) and MOB4 (MOB family member 4, phocein) genes on chromosome 2. The read-through transcript produces a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 2-197500319-C-G is Benign according to our data. Variant chr2-197500319-C-G is described in ClinVar as Benign. ClinVar VariationId is 1271798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000409729.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPE1	NM_002157.3	MANE Select	c.-118C>G		upstream_gene	N/A	NP_002148.1	P61604
	HSPD1	NM_199440.2		c.-162G>C		upstream_gene	N/A	NP_955472.1	A0A024R3X4
	HSPE1-MOB4	NM_001202485.2		c.-118C>G		upstream_gene	N/A	NP_001189414.1	S4R3N1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPE1	ENST00000915249.1		c.-118C>G		5_prime_UTR	Exon 1 of 4	ENSP00000585308.1
	HSPE1	ENST00000915250.1		c.-118C>G		5_prime_UTR	Exon 1 of 4	ENSP00000585309.1
	HSPE1	ENST00000915248.1		c.-118C>G		5_prime_UTR	Exon 1 of 4	ENSP00000585307.1

Frequencies

GnomAD3 genomes AF: 0.684 AC: 103719 AN: 151714 Hom.: 35849 Cov.: 33

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.863

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.707

GnomAD4 exome AF: 0.672 AC: 904201 AN: 1346006 Hom.: 305074 Cov.: 21 AF XY: 0.673 AC XY: 448628 AN XY: 666250

African (AFR) AF: 0.762 AC: 23308 AN: 30596

American (AMR) AF: 0.534 AC: 18906 AN: 35386

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 18489 AN: 24722

East Asian (EAS) AF: 0.559 AC: 19868 AN: 35568

South Asian (SAS) AF: 0.708 AC: 55260 AN: 78052

European-Finnish (FIN) AF: 0.580 AC: 28031 AN: 48332

Middle Eastern (MID) AF: 0.848 AC: 3559 AN: 4198

European-Non Finnish (NFE) AF: 0.676 AC: 698761 AN: 1033056

Other (OTH) AF: 0.678 AC: 38019 AN: 56096

GnomAD4 genome AF: 0.684 AC: 103803 AN: 151834 Hom.: 35878 Cov.: 33 AF XY: 0.680 AC XY: 50476 AN XY: 74226

African (AFR) AF: 0.755 AC: 31328 AN: 41468

American (AMR) AF: 0.644 AC: 9848 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 2593 AN: 3466

East Asian (EAS) AF: 0.504 AC: 2564 AN: 5086

South Asian (SAS) AF: 0.694 AC: 3348 AN: 4824

European-Finnish (FIN) AF: 0.571 AC: 6035 AN: 10564

Middle Eastern (MID) AF: 0.866 AC: 253 AN: 292

European-Non Finnish (NFE) AF: 0.674 AC: 45695 AN: 67824

Other (OTH) AF: 0.707 AC: 1490 AN: 2108

Alfa AF: 0.530 Hom.: 1371

Bravo AF: 0.689

Asia WGS AF: 0.610 AC: 2124 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.2
DANN	Benign	0.50
PhyloP100		-0.16
PromoterAI		0.014	Neutral
Mutation Taster		=289/11	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1116734; hg19: chr2-198365043; COSMIC: COSV52098402; COSMIC: COSV52098402;