chr5-133052346-C-T

Variant names:

• chr5-133052346-C-T
• rs143631835
• NM_002154.4:c.96C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.67
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 725437.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 179 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002154.4. 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
	HSPA4	NM_002154.4	MANE Select	c.96C>T	p.Asp32Asp	synonymous	Exon 1 of 19	NP_002145.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA4	ENST00000304858.7	TSL:1 MANE Select	c.96C>T	p.Asp32Asp	synonymous	Exon 1 of 19	ENSP00000302961.2	P34932-1
	HSPA4	ENST00000968145.1		c.96C>T	p.Asp32Asp	synonymous	Exon 1 of 20	ENSP00000638204.1
	HSPA4	ENST00000936301.1		c.96C>T	p.Asp32Asp	synonymous	Exon 1 of 19	ENSP00000606360.1

Frequencies

GnomAD3 genomes AF: 0.00118 AC: 179 AN: 152222 Hom.: 0 Cov.: 33

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

GnomAD2 exomes AF: 0.000957 AC: 157 AN: 164032 AF XY: 0.000852

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 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.: 4 Cov.: 29 AF XY: 0.00137 AC XY: 950 AN XY: 694206

African (AFR) AF: 0.000221 AC: 7 AN: 31704

American (AMR) AF: 0.000316 AC: 12 AN: 37936

Ashkenazi Jewish (ASJ) AF: 0.000639 AC: 16 AN: 25054

East Asian (EAS) AF: 0.0000274 AC: 1 AN: 36470

South Asian (SAS) AF: 0.00 AC: 0 AN: 81132

European-Finnish (FIN) AF: 0.000212 AC: 9 AN: 42458

Middle Eastern (MID) AF: 0.000178 AC: 1 AN: 5604

European-Non Finnish (NFE) AF: 0.00177 AC: 1917 AN: 1082746

Other (OTH) AF: 0.000808 AC: 47 AN: 58140

GnomAD4 genome AF: 0.00118 AC: 179 AN: 152340 Hom.: 0 Cov.: 33 AF XY: 0.000886 AC XY: 66 AN XY: 74486

African (AFR) AF: 0.000361 AC: 15 AN: 41596

American (AMR) AF: 0.00111 AC: 17 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00209 AC: 142 AN: 68028

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00180 Hom.: 0

Bravo AF: 0.00123

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	15
DANN	Benign	0.96
PhyloP100		3.7
PromoterAI		0.072	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs143631835; hg19: chr5-132388038;