dbSNP rs4713489: HSPA1L:c.-291C>T (chr6-31815166-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005527.4(HSPA1L):c.-291C>T variant causes a 5 prime UTR premature start codon gain 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_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.06

Publications

7 publications found

Variant links:

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]

HSPA1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HSPA1L	NM_005527.4 link	c.-291C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	ENST00000375654.5	NP_005518.3
HSPA1L	NM_005527.4 link	c.-291C>T		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 link	c.-291C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	1	NM_005527.4	ENSP00000364805.4
HSPA1L	ENST00000375654.5 link	c.-291C>T		5_prime_UTR_variant	Exon 1 of 2	1	NM_005527.4	ENSP00000364805.4

Frequencies

GnomAD3 genomes

AF:

0.0415

AC:

6257

AN:

150632

Hom.:

181

Cov.:

show subpopulations

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.:

AF XY:

0.0207

AC XY:

1065

AN XY:

51376

show subpopulations

African (AFR)

AF:

0.0572

AC:

AN:

1714

American (AMR)

AF:

0.0536

AC:

AN:

1846

Ashkenazi Jewish (ASJ)

AF:

0.00763

AC:

AN:

786

East Asian (EAS)

AF:

0.00898

AC:

AN:

1114

South Asian (SAS)

AF:

0.0406

AC:

180

AN:

4436

European-Finnish (FIN)

AF:

0.00988

AC:

AN:

506

Middle Eastern (MID)

AF:

0.0231

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.0174

AC:

1586

AN:

90910

Other (OTH)

AF:

0.0216

AC:

AN:

3750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

107

214

322

429

536

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

240

320

400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0415

AC:

6257

AN:

150742

Hom.:

181

Cov.:

AF XY:

0.0414

AC XY:

3043

AN XY:

73574

show subpopulations

African (AFR)

AF:

0.0831

AC:

3402

AN:

40926

American (AMR)

AF:

0.0305

AC:

462

AN:

15130

Ashkenazi Jewish (ASJ)

AF:

0.0113

AC:

AN:

3448

East Asian (EAS)

AF:

0.0140

AC:

AN:

5160

South Asian (SAS)

AF:

0.0396

AC:

189

AN:

4770

European-Finnish (FIN)

AF:

0.0159

AC:

165

AN:

10350

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0270

AC:

1829

AN:

67660

Other (OTH)

AF:

0.0401

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

275

549

824

1098

1373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0351

Hom.:

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

(source)

DANN

Benign

0.90

PhyloP100

-2.1

PromoterAI

0.054

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over