rs4713489

Positions:

• chr6-31815166-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005527.4(HSPA1L):​c.-291C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0325 in 256,020 control chromosomes in the GnomAD database, including 222 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 0.042 (181 hom., cov: 30)
  • Exomes 𝑓: 0.020 (41 hom.)
• Consequence: HSPA1L NM_005527.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

Genes affected

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPA1L	NM_005527.4	c.-291C>T		5_prime_UTR_variant	1/2	ENST00000375654.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPA1L	ENST00000375654.5	c.-291C>T		5_prime_UTR_variant	1/2	1	NM_005527.4	P1

Frequencies

GnomAD3 genomes AF: 0.0415 AC: 6257 AN: 150632 Hom.: 181 Cov.: 30

Gnomad AFR AF: 0.0833

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0306

Gnomad ASJ AF: 0.0113

Gnomad EAS AF: 0.0139

Gnomad SAS AF: 0.0394

Gnomad FIN AF: 0.0159

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0270

Gnomad OTH AF: 0.0405

GnomAD4 exome AF: 0.0197 AC: 2070 AN: 105278 Hom.: 41 AF XY: 0.0207 AC XY: 1065 AN XY: 51376

Gnomad4 AFR exome AF: 0.0572

Gnomad4 AMR exome AF: 0.0536

Gnomad4 ASJ exome AF: 0.00763

Gnomad4 EAS exome AF: 0.00898

Gnomad4 SAS exome AF: 0.0406

Gnomad4 FIN exome AF: 0.00988

Gnomad4 NFE exome AF: 0.0174

Gnomad4 OTH exome AF: 0.0216

GnomAD4 genome AF: 0.0415 AC: 6257 AN: 150742 Hom.: 181 Cov.: 30 AF XY: 0.0414 AC XY: 3043 AN XY: 73574

Gnomad4 AFR AF: 0.0831

Gnomad4 AMR AF: 0.0305

Gnomad4 ASJ AF: 0.0113

Gnomad4 EAS AF: 0.0140

Gnomad4 SAS AF: 0.0396

Gnomad4 FIN AF: 0.0159

Gnomad4 NFE AF: 0.0270

Gnomad4 OTH AF: 0.0401

Alfa AF: 0.0364 Hom.: 21

Bravo AF: 0.0436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.90

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4713489; hg19: chr6-31782943;