chr6-31815660-T-C

Variant names:

• chr6-31815660-T-C
• rs11557922
• NM_005345.6:c.-97T>C

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.-97T>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 0.0223 in 1,612,906 control chromosomes in the GnomAD database, including 543 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 0.028 (84 hom., cov: 32)
  • Exomes 𝑓: 0.022 (459 hom.)
• Consequence: HSPA1A NM_005345.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 6 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=-0.49).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0282 (4299/152354) while in subpopulation AMR AF = 0.0487 (745/15304). AF 95% confidence interval is 0.0458. There are 84 homozygotes in GnomAd4. There are 2057 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4299 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.-97T>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.-97T>C		5_prime_UTR	Exon 1 of 1	ENSP00000364802.5
	HSPA1A	ENST00000608703.2	TSL:2	c.-97T>C		5_prime_UTR	Exon 1 of 2	ENSP00000477378.1

Frequencies

GnomAD3 genomes AF: 0.0283 AC: 4309 AN: 152236 Hom.: 84 Cov.: 32

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0487

Gnomad ASJ AF: 0.0449

Gnomad EAS AF: 0.00943

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.00282

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0223

Gnomad OTH AF: 0.0392

GnomAD4 exome AF: 0.0216 AC: 31621 AN: 1460552 Hom.: 459 Cov.: 31 AF XY: 0.0214 AC XY: 15563 AN XY: 726588

African (AFR) AF: 0.0428 AC: 1434 AN: 33466

American (AMR) AF: 0.0339 AC: 1513 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.0461 AC: 1205 AN: 26116

East Asian (EAS) AF: 0.00383 AC: 152 AN: 39692

South Asian (SAS) AF: 0.0167 AC: 1440 AN: 86226

European-Finnish (FIN) AF: 0.00334 AC: 175 AN: 52430

Middle Eastern (MID) AF: 0.0427 AC: 246 AN: 5766

European-Non Finnish (NFE) AF: 0.0216 AC: 24043 AN: 1111828

Other (OTH) AF: 0.0234 AC: 1413 AN: 60362

GnomAD4 genome AF: 0.0282 AC: 4299 AN: 152354 Hom.: 84 Cov.: 32 AF XY: 0.0276 AC XY: 2057 AN XY: 74504

African (AFR) AF: 0.0393 AC: 1635 AN: 41582

American (AMR) AF: 0.0487 AC: 745 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0449 AC: 156 AN: 3472

East Asian (EAS) AF: 0.00945 AC: 49 AN: 5186

South Asian (SAS) AF: 0.0145 AC: 70 AN: 4830

European-Finnish (FIN) AF: 0.00282 AC: 30 AN: 10630

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0223 AC: 1515 AN: 68028

Other (OTH) AF: 0.0383 AC: 81 AN: 2116

Alfa AF: 0.0236 Hom.: 87

Bravo AF: 0.0330

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	3.7
DANN	Benign	0.64
PhyloP100		-1.5
PromoterAI		-0.22	Neutral
Mutation Taster		=300/0	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: rs11557922; hg19: chr6-31783437;