chr6-31815166-G-C

Variant names:

• chr6-31815166-G-C
• rs4713489
• NM_005527.4:c.-291C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005527.4(HSPA1L):​c.-291C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000399 in 105,282 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. 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: not found (cov: 30)
  • Exomes 𝑓: 0.00040 (0 hom.)
• Consequence: HSPA1L NM_005527.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPA1L	NM_005527.4	c.-291C>G		5_prime_UTR_variant	Exon 1 of 2	ENST00000375654.5	NP_005518.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA1L	ENST00000375654.5	c.-291C>G		5_prime_UTR_variant	Exon 1 of 2	1	NM_005527.4	ENSP00000364805.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.000399 AC: 42 AN: 105282 Hom.: 0 AF XY: 0.000370 AC XY: 19 AN XY: 51374

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 1714

American (AMR) AF: 0.00870 AC: 16 AN: 1840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 786

East Asian (EAS) AF: 0.00269 AC: 3 AN: 1114

South Asian (SAS) AF: 0.00270 AC: 12 AN: 4438

European-Finnish (FIN) AF: 0.00198 AC: 1 AN: 506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.000110 AC: 10 AN: 90916

Other (OTH) AF: 0.00 AC: 0 AN: 3752

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.95
DANN	Benign	0.49
PhyloP100		-2.1
PromoterAI		0.12	Neutral

Splicing

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

Other links and lift over

dbSNP: rs4713489; hg19: chr6-31782943;