Variant 6-31810752-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_005527.4(HSPA1L):c.1221G>A(p.Thr407=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0844 in 1,613,840 control chromosomes in the GnomAD database, including 7,793 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.13 ( 1599 hom., cov: 32)

Exomes 𝑓: 0.080 ( 6194 hom. )

Consequence

HSPA1L
NM_005527.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -9.35

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 6-31810752-C-T is Benign according to our data. Variant chr6-31810752-C-T is described in ClinVar as [Benign]. Clinvar id is 3059212.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-9.35 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPA1L	NM_005527.4 linkuse as main transcript	c.1221G>A	p.Thr407=	synonymous_variant	2/2	ENST00000375654.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPA1L	ENST00000375654.5 linkuse as main transcript	c.1221G>A	p.Thr407=	synonymous_variant	2/2	1	NM_005527.4	P1

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19142

AN:

151848

Hom.:

1592

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.141

Gnomad ASJ

AF:

0.223

Gnomad EAS

AF:

0.177

Gnomad SAS

AF:

0.0955

Gnomad FIN

AF:

0.0422

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.0757

Gnomad OTH

AF:

0.157

GnomAD3 exomes

AF:

0.103

AC:

25959

AN:

251410

Hom.:

1898

AF XY:

0.0982

AC XY:

13342

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.218

Gnomad AMR exome

AF:

0.125

Gnomad ASJ exome

AF:

0.224

Gnomad EAS exome

AF:

0.180

Gnomad SAS exome

AF:

0.0794

Gnomad FIN exome

AF:

0.0408

Gnomad NFE exome

AF:

0.0744

Gnomad OTH exome

AF:

0.123

GnomAD4 exome

AF:

0.0800

AC:

116982

AN:

1461874

Hom.:

6194

Cov.:

AF XY:

0.0798

AC XY:

58070

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.218

Gnomad4 AMR exome

AF:

0.130

Gnomad4 ASJ exome

AF:

0.226

Gnomad4 EAS exome

AF:

0.155

Gnomad4 SAS exome

AF:

0.0821

Gnomad4 FIN exome

AF:

0.0408

Gnomad4 NFE exome

AF:

0.0680

Gnomad4 OTH exome

AF:

0.101

GnomAD4 genome

AF:

0.126

AC:

19164

AN:

151966

Hom.:

1599

Cov.:

AF XY:

0.125

AC XY:

9286

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.214

Gnomad4 AMR

AF:

0.141

Gnomad4 ASJ

AF:

0.223

Gnomad4 EAS

AF:

0.176

Gnomad4 SAS

AF:

0.0956

Gnomad4 FIN

AF:

0.0422

Gnomad4 NFE

AF:

0.0757

Gnomad4 OTH

AF:

0.156

Alfa

AF:

0.0988

Hom.:

1779

Bravo

AF:

0.141

Asia WGS

AF:

0.119

AC:

414

AN:

3478

EpiCase

AF:

0.0883

EpiControl

AF:

0.0908

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HSPA1L-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.019

DANN

Benign

0.48

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over