6-31815730-G-C

Variant names:

• chr6-31815730-G-C
• rs1043618
• NM_005345.6:c.-27G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005345.6(HSPA1A):​c.-27G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 1,613,618 control chromosomes in the GnomAD database, including 131,593 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.48 (19690 hom., cov: 32)
  • Exomes 𝑓: 0.38 (111903 hom.)
• Consequence: HSPA1A NM_005345.6 5_prime_UTR
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -1.28
• Publications: 129 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

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.-27G>C		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.-27G>C		5_prime_UTR	Exon 1 of 1	ENSP00000364802.5
	HSPA1A	ENST00000608703.2	TSL:2	c.-27G>C		5_prime_UTR	Exon 1 of 2	ENSP00000477378.1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73138 AN: 152022 Hom.: 19663 Cov.: 32

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.488

GnomAD2 exomes AF: 0.389 AC: 97716 AN: 250976 AF XY: 0.386

Gnomad AFR exome AF: 0.745

Gnomad AMR exome AF: 0.289

Gnomad ASJ exome AF: 0.365

Gnomad EAS exome AF: 0.307

Gnomad FIN exome AF: 0.461

Gnomad NFE exome AF: 0.370

Gnomad OTH exome AF: 0.396

GnomAD4 exome AF: 0.384 AC: 561510 AN: 1461478 Hom.: 111903 Cov.: 92 AF XY: 0.383 AC XY: 278473 AN XY: 727062

African (AFR) AF: 0.750 AC: 25097 AN: 33480

American (AMR) AF: 0.304 AC: 13594 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 9650 AN: 26126

East Asian (EAS) AF: 0.243 AC: 9647 AN: 39698

South Asian (SAS) AF: 0.396 AC: 34136 AN: 86242

European-Finnish (FIN) AF: 0.461 AC: 24507 AN: 53104

Middle Eastern (MID) AF: 0.415 AC: 2395 AN: 5766

European-Non Finnish (NFE) AF: 0.376 AC: 417955 AN: 1111956

Other (OTH) AF: 0.406 AC: 24529 AN: 60388

GnomAD4 genome AF: 0.481 AC: 73202 AN: 152140 Hom.: 19690 Cov.: 32 AF XY: 0.480 AC XY: 35671 AN XY: 74376

African (AFR) AF: 0.736 AC: 30529 AN: 41504

American (AMR) AF: 0.369 AC: 5647 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1266 AN: 3472

East Asian (EAS) AF: 0.294 AC: 1520 AN: 5162

South Asian (SAS) AF: 0.421 AC: 2032 AN: 4826

European-Finnish (FIN) AF: 0.481 AC: 5089 AN: 10576

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25722 AN: 67990

Other (OTH) AF: 0.489 AC: 1033 AN: 2112

Alfa AF: 0.304 Hom.: 1183

Bravo AF: 0.484

Asia WGS AF: 0.423 AC: 1470 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Chronic obstructive pulmonary disease Other:1

Aug 04, 2019

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance: association

Review Status: no assertion criteria provided

Collection Method: case-control

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.61
DANN	Benign	0.51
PhyloP100		-1.3
PromoterAI		0.0096	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=296/4	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: rs1043618; hg19: chr6-31783507; COSMIC: COSV65149271; COSMIC: COSV65149271;