6-31810530-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005527.4(HSPA1L):c.1443C>T(p.Asp481=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00571 in 1,613,116 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 122 hom. )

Consequence

HSPA1L
NM_005527.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.73

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 6-31810530-G-A is Benign according to our data. Variant chr6-31810530-G-A is described in ClinVar as [Benign]. Clinvar id is 783631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.73 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00577 (8423/1460868) while in subpopulation EAS AF= 0.0443 (1758/39696). AF 95% confidence interval is 0.0426. There are 122 homozygotes in gnomad4_exome. There are 4512 alleles in male gnomad4_exome subpopulation. Median coverage is 36. This position pass quality control queck.

BS2

High AC in GnomAd at 781 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPA1L	NM_005527.4 linkuse as main transcript	c.1443C>T	p.Asp481=	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.1443C>T	p.Asp481=	synonymous_variant	2/2	1	NM_005527.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00513

AC:

781

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000797

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00681

Gnomad ASJ

AF:

0.0374

Gnomad EAS

AF:

0.0152

Gnomad SAS

AF:

0.0131

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00503

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00725

AC:

1813

AN:

250234

Hom.:

AF XY:

0.00811

AC XY:

1096

AN XY:

135220

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00457

Gnomad ASJ exome

AF:

0.0396

Gnomad EAS exome

AF:

0.0130

Gnomad SAS exome

AF:

0.0121

Gnomad FIN exome

AF:

0.000420

Gnomad NFE exome

AF:

0.00505

Gnomad OTH exome

AF:

0.0116

GnomAD4 exome

AF:

0.00577

AC:

8423

AN:

1460868

Hom.:

122

Cov.:

AF XY:

0.00621

AC XY:

4512

AN XY:

726680

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00492

Gnomad4 ASJ exome

AF:

0.0414

Gnomad4 EAS exome

AF:

0.0443

Gnomad4 SAS exome

AF:

0.0122

Gnomad4 FIN exome

AF:

0.000675

Gnomad4 NFE exome

AF:

0.00328

Gnomad4 OTH exome

AF:

0.00759

GnomAD4 genome

AF:

0.00513

AC:

781

AN:

152248

Hom.:

Cov.:

AF XY:

0.00558

AC XY:

415

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.000795

Gnomad4 AMR

AF:

0.00680

Gnomad4 ASJ

AF:

0.0374

Gnomad4 EAS

AF:

0.0152

Gnomad4 SAS

AF:

0.0131

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00503

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00781

Hom.:

Bravo

AF:

0.00535

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	HSPA1L: BP4, BP7, BS1, BS2 -

HSPA1L-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 30, 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

-0.51

Cadd

Benign

3.0

Dann

Benign

0.85

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