Variant 5-133052346-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_002154.4(HSPA4):c.96C>T(p.Asp32Asp) variant causes a synonymous change. The variant allele was found at a frequency of 0.00141 in 1,553,584 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 4 hom. )

Consequence

HSPA4
NM_002154.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.67

Variant links:

Genes affected

HSPA4 (HGNC:5237): (heat shock protein family A (Hsp70) member 4) Predicted to enable ATP binding activity. Involved in chaperone-mediated protein complex assembly and protein insertion into mitochondrial outer membrane. Located in cytosol and extracellular exosome. Implicated in Chagas disease. Biomarker of chronic obstructive pulmonary disease; rheumatoid arthritis; type 2 diabetes mellitus; and ulcerative colitis. [provided by Alliance of Genome Resources, Apr 2022]

HSPA4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 5-133052346-C-T is Benign according to our data. Variant chr5-133052346-C-T is described in ClinVar as [Benign]. Clinvar id is 725437.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 179 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPA4	NM_002154.4 linkuse as main transcript	c.96C>T	p.Asp32Asp	synonymous_variant	1/19	ENST00000304858.7	NP_002145.3	P34932-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA4	ENST00000304858.7 linkuse as main transcript	c.96C>T	p.Asp32Asp	synonymous_variant	1/19	1	NM_002154.4	ENSP00000302961.2		P34932-1

Frequencies

GnomAD3 genomes

AF:

0.00118

AC:

179

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00209

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000957

AC:

157

AN:

164032

Hom.:

AF XY:

0.000852

AC XY:

AN XY:

89222

show subpopulations

Gnomad AFR exome

AF:

0.000318

Gnomad AMR exome

AF:

0.000382

Gnomad ASJ exome

AF:

0.000361

Gnomad EAS exome

AF:

0.0000814

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000940

Gnomad NFE exome

AF:

0.00201

Gnomad OTH exome

AF:

0.000442

GnomAD4 exome

AF:

0.00143

AC:

2010

AN:

1401244

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

950

AN XY:

694206

show subpopulations

Gnomad4 AFR exome

AF:

0.000221

Gnomad4 AMR exome

AF:

0.000316

Gnomad4 ASJ exome

AF:

0.000639

Gnomad4 EAS exome

AF:

0.0000274

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000212

Gnomad4 NFE exome

AF:

0.00177

Gnomad4 OTH exome

AF:

0.000808

GnomAD4 genome

AF:

0.00118

AC:

179

AN:

152340

Hom.:

Cov.:

AF XY:

0.000886

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00209

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00180

Hom.:

Bravo

AF:

0.00123

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.96

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over