dbSNP rs746807103: HSBP1L1:p.Ala8Asp (chr18-79964758-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001136180.2(HSBP1L1):c.23C>A(p.Ala8Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000779 in 1,412,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000084 ( 0 hom. )

Consequence

HSBP1L1
NM_001136180.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.57

Variant links:

Genes affected

HSBP1L1 (HGNC:37243): (heat shock factor binding protein 1 like 1) Predicted to enable transcription corepressor activity. Predicted to be involved in cellular heat acclimation. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

HSBP1L1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.017536074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSBP1L1	NM_001136180.2 link	c.23C>A	p.Ala8Asp	missense_variant	Exon 1 of 4	ENST00000451882.3	NP_001129652.1	C9JCN9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HSBP1L1	ENST00000451882.3 link	c.23C>A	p.Ala8Asp	missense_variant	Exon 1 of 4	1	NM_001136180.2	ENSP00000414236.1	C9JCN9
HSBP1L1	ENST00000589516.1 link	n.23C>A		non_coding_transcript_exon_variant	Exon 1 of 4	3		ENSP00000467108.1	K7ENV5
HSBP1L1	ENST00000592352.1 link	n.177C>A		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151634

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000590

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000640

AC:

AN:

46888

Hom.:

AF XY:

0.000109

AC XY:

AN XY:

27640

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000865

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000841

AC:

106

AN:

1261000

Hom.:

Cov.:

AF XY:

0.0000759

AC XY:

AN XY:

619526

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000155

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000102

Gnomad4 OTH exome

AF:

0.0000193

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151634

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74070

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000590

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.000140

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.23C>A (p.A8D) alteration is located in exon 1 (coding exon 1) of the HSBP1L1 gene. This alteration results from a C to A substitution at nucleotide position 23, causing the alanine (A) at amino acid position 8 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

8.0

DANN

Benign

0.94

DEOGEN2

Benign

0.0042

Eigen

Benign

-0.90

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.43

M_CAP

Benign

0.019

MetaRNN

Benign

0.018

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.75

PROVEAN

Benign

0.37

REVEL

Benign

0.032

Sift

Benign

0.043

Sift4G

Benign

0.069

Polyphen

0.33

Vest4

0.075

MVP

0.030

ClinPred

0.051

GERP RS

-0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.068

gMVP

0.083

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