dbSNP rs1461496: HSPA8:c.-107T>C (chr11-123058916-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000526686.1(HSPA8):c.-107T>C 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 0.644 in 1,428,906 control chromosomes in the GnomAD database, including 300,336 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 0.71 ( 39732 hom., cov: 33)

Exomes 𝑓: 0.64 ( 260604 hom. )

Consequence

HSPA8
ENST00000526686.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.74

Publications

15 publications found

Variant links:

Genes affected

HSPA8 (HGNC:5241): (heat shock protein family A (Hsp70) member 8) This gene encodes a member of the heat shock protein 70 family, which contains both heat-inducible and constitutively expressed members. This protein belongs to the latter group, which are also referred to as heat-shock cognate proteins. It functions as a chaperone, and binds to nascent polypeptides to facilitate correct folding. It also functions as an ATPase in the disassembly of clathrin-coated vesicles during transport of membrane components through the cell. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

HSPA8 links:

SNORD14D (HGNC:30353): (small nucleolar RNA, C/D box 14D)

SNORD14D links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000526686.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.47).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000526686.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HSPA8	NM_006597.6	MANE Select	c.1324-86T>C	intron	N/A	NP_006588.1	P11142-1
HSPA8	NM_153201.4		c.1324-86T>C	intron	N/A	NP_694881.1	P11142-2
SNORD14D	NR_001454.2		n.80T>C	non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HSPA8	ENST00000526686.1	TSL:1	c.-107T>C	5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000435019.1	E9PM13
HSPA8	ENST00000526686.1	TSL:1	c.-107T>C	5_prime_UTR	Exon 1 of 3	ENSP00000435019.1	E9PM13
HSPA8	ENST00000534624.6	TSL:1 MANE Select	c.1324-86T>C	intron	N/A	ENSP00000432083.1	P11142-1

Frequencies

GnomAD3 genomes

AF:

0.709

AC:

107901

AN:

152092

Hom.:

39675

Cov.:

show subpopulations

Gnomad AFR

AF:

0.922

Gnomad AMI

AF:

0.715

Gnomad AMR

AF:

0.645

Gnomad ASJ

AF:

0.638

Gnomad EAS

AF:

0.589

Gnomad SAS

AF:

0.624

Gnomad FIN

AF:

0.599

Gnomad MID

AF:

0.680

Gnomad NFE

AF:

0.632

Gnomad OTH

AF:

0.684

GnomAD4 exome

AF:

0.636

AC:

812399

AN:

1276696

Hom.:

260604

Cov.:

AF XY:

0.635

AC XY:

407542

AN XY:

641550

show subpopulations

African (AFR)

AF:

0.930

AC:

27734

AN:

29820

American (AMR)

AF:

0.644

AC:

26050

AN:

40458

Ashkenazi Jewish (ASJ)

AF:

0.634

AC:

15359

AN:

24242

East Asian (EAS)

AF:

0.578

AC:

22218

AN:

38426

South Asian (SAS)

AF:

0.624

AC:

50475

AN:

80950

European-Finnish (FIN)

AF:

0.602

AC:

31329

AN:

52014

Middle Eastern (MID)

AF:

0.670

AC:

3615

AN:

5398

European-Non Finnish (NFE)

AF:

0.632

AC:

600902

AN:

951278

Other (OTH)

AF:

0.642

AC:

34717

AN:

54110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

16023

32046

48069

64092

80115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15194

30388

45582

60776

75970

<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:

0.710

AC:

108020

AN:

152210

Hom.:

39732

Cov.:

AF XY:

0.704

AC XY:

52398

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.922

AC:

38294

AN:

41554

American (AMR)

AF:

0.644

AC:

9848

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.638

AC:

2216

AN:

3472

East Asian (EAS)

AF:

0.589

AC:

3053

AN:

5180

South Asian (SAS)

AF:

0.625

AC:

3018

AN:

4830

European-Finnish (FIN)

AF:

0.599

AC:

6351

AN:

10594

Middle Eastern (MID)

AF:

0.684

AC:

201

AN:

294

European-Non Finnish (NFE)

AF:

0.632

AC:

42939

AN:

67976

Other (OTH)

AF:

0.685

AC:

1448

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1526

3052

4577

6103

7629

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

820

1640

2460

3280

4100

<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:

0.661

Hom.:

26142

Bravo

AF:

0.725

Asia WGS

AF:

0.602

AC:

2091

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

1.7

PromoterAI

0.0021

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over