rs34397183

Variant names:

• chr6-31815566-G-A
• rs34397183
• NM_005345.6:c.-191G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_005345.6(HSPA1A):​c.-191G>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 0.0017 in 1,378,072 control chromosomes in the GnomAD database, including 31 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 0.0077 (20 hom., cov: 32)
  • Exomes 𝑓: 0.00095 (11 hom.)
• Consequence: HSPA1A NM_005345.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0077 (1173/152352) while in subpopulation AFR AF = 0.0267 (1108/41572). AF 95% confidence interval is 0.0253. There are 20 homozygotes in GnomAd4. There are 527 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1173 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA1A	NM_005345.6	MANE Select	c.-191G>A		5_prime_UTR	Exon 1 of 1	NP_005336.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA1A	ENST00000375651.7	TSL:6 MANE Select	c.-191G>A		5_prime_UTR	Exon 1 of 1	ENSP00000364802.5
	HSPA1A	ENST00000608703.2	TSL:2	c.-191G>A		5_prime_UTR	Exon 1 of 2	ENSP00000477378.1
	HSPA1L	ENST00000879288.1		c.-14+15C>T		intron	N/A	ENSP00000549347.1

Frequencies

GnomAD3 genomes AF: 0.00768 AC: 1169 AN: 152234 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.0266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00430

GnomAD4 exome AF: 0.000953 AC: 1168 AN: 1225720 Hom.: 11 Cov.: 19 AF XY: 0.000848 AC XY: 520 AN XY: 613398

African (AFR) AF: 0.0259 AC: 722 AN: 27836

American (AMR) AF: 0.00186 AC: 65 AN: 35024

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23736

East Asian (EAS) AF: 0.00 AC: 0 AN: 35206

South Asian (SAS) AF: 0.0000916 AC: 7 AN: 76434

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38812

Middle Eastern (MID) AF: 0.000186 AC: 1 AN: 5386

European-Non Finnish (NFE) AF: 0.000313 AC: 291 AN: 931030

Other (OTH) AF: 0.00157 AC: 82 AN: 52256

GnomAD4 genome AF: 0.00770 AC: 1173 AN: 152352 Hom.: 20 Cov.: 32 AF XY: 0.00707 AC XY: 527 AN XY: 74502

African (AFR) AF: 0.0267 AC: 1108 AN: 41572

American (AMR) AF: 0.00242 AC: 37 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68040

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00416 Hom.: 9

Bravo AF: 0.00886

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	1.2
DANN	Benign	0.73
PhyloP100		-1.3
PromoterAI		0.0058	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.3
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: rs34397183; hg19: chr6-31783343;