chr6-31815599-C-A

Variant names:

• chr6-31815599-C-A
• rs33934112
• NM_005345.6:c.-158C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_005345.6(HSPA1A):​c.-158C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,552,412 control chromosomes in the GnomAD database, including 164 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 0.0087 (7 hom., cov: 32)
  • Exomes 𝑓: 0.011 (157 hom.)
• Consequence: HSPA1A NM_005345.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100
• Publications: 4 publications found

Genes affected

HSPA1A (HGNC:5232): (heat shock protein family A (Hsp70) member 1A) This intronless gene encodes a 70kDa heat shock protein which is a member of the heat shock protein 70 family. In conjuction with other heat shock proteins, this protein stabilizes existing proteins against aggregation and mediates the folding of newly translated proteins in the cytosol and in organelles. It is also involved in the ubiquitin-proteasome pathway through interaction with the AU-rich element RNA-binding protein 1. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which encode similar proteins. [provided by RefSeq, Jul 2008]

HSPA1L (HGNC:5234): (heat shock protein family A (Hsp70) member 1 like) This gene encodes a 70kDa heat shock protein. In conjunction with other heat shock proteins, this protein stabilizes existing proteins against aggregation and mediates the folding of newly translated proteins in the cytosol and in organelles. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which also encode isoforms of the 70kDa heat shock protein. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00867 (1321/152346) while in subpopulation SAS AF = 0.0348 (168/4828). AF 95% confidence interval is 0.0305. There are 7 homozygotes in GnomAd4. There are 694 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1321 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005345.6. 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
	HSPA1A	NM_005345.6	MANE Select	c.-158C>A		5_prime_UTR	Exon 1 of 1	NP_005336.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA1A	ENST00000375651.7	TSL:6 MANE Select	c.-158C>A		5_prime_UTR	Exon 1 of 1	ENSP00000364802.5
	HSPA1L	ENST00000879288.1		c.-32G>T		5_prime_UTR	Exon 1 of 2	ENSP00000549347.1
	HSPA1A	ENST00000608703.2	TSL:2	c.-158C>A		5_prime_UTR	Exon 1 of 2	ENSP00000477378.1

Frequencies

GnomAD3 genomes AF: 0.00867 AC: 1320 AN: 152228 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00369

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00811

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.0346

Gnomad FIN AF: 0.00885

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00999

Gnomad OTH AF: 0.00716

GnomAD4 exome AF: 0.0109 AC: 15293 AN: 1400066 Hom.: 157 Cov.: 26 AF XY: 0.0120 AC XY: 8345 AN XY: 696830

African (AFR) AF: 0.00318 AC: 101 AN: 31790

American (AMR) AF: 0.00479 AC: 191 AN: 39912

Ashkenazi Jewish (ASJ) AF: 0.00820 AC: 209 AN: 25490

East Asian (EAS) AF: 0.00660 AC: 252 AN: 38206

South Asian (SAS) AF: 0.0383 AC: 3176 AN: 82916

European-Finnish (FIN) AF: 0.00959 AC: 458 AN: 47758

Middle Eastern (MID) AF: 0.0151 AC: 86 AN: 5682

European-Non Finnish (NFE) AF: 0.00944 AC: 10106 AN: 1070056

Other (OTH) AF: 0.0123 AC: 714 AN: 58256

GnomAD4 genome AF: 0.00867 AC: 1321 AN: 152346 Hom.: 7 Cov.: 32 AF XY: 0.00932 AC XY: 694 AN XY: 74500

African (AFR) AF: 0.00368 AC: 153 AN: 41582

American (AMR) AF: 0.00810 AC: 124 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00836 AC: 29 AN: 3470

East Asian (EAS) AF: 0.0102 AC: 53 AN: 5188

South Asian (SAS) AF: 0.0348 AC: 168 AN: 4828

European-Finnish (FIN) AF: 0.00885 AC: 94 AN: 10620

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0100 AC: 681 AN: 68034

Other (OTH) AF: 0.00709 AC: 15 AN: 2116

Alfa AF: 0.00611 Hom.: 0

Bravo AF: 0.00770

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	4.2
DANN	Benign	0.56
PhyloP100		0.10
PromoterAI		0.066	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Mutation Taster		=300/0	polymorphism

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: rs33934112; hg19: chr6-31783376; COSMIC: COSV107483708; COSMIC: COSV107483708;