chr18-79964758-C-T

Variant names:

• chr18-79964758-C-T
• rs746807103
• NM_001136180.2:c.23C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001136180.2(HSBP1L1):​c.23C>T​(p.Ala8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000159 in 1,261,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A8D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: HSBP1L1 NM_001136180.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.57
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037855804).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136180.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSBP1L1	NM_001136180.2	MANE Select	c.23C>T	p.Ala8Val	missense	Exon 1 of 4	NP_001129652.1	C9JCN9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSBP1L1	ENST00000451882.3	TSL:1 MANE Select	c.23C>T	p.Ala8Val	missense	Exon 1 of 4	ENSP00000414236.1	C9JCN9
	HSBP1L1	ENST00000903187.1		c.23C>T	p.Ala8Val	missense	Exon 1 of 3	ENSP00000573246.1
	HSBP1L1	ENST00000903186.1		c.23C>T	p.Ala8Val	missense	Exon 1 of 2	ENSP00000573245.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000159 AC: 2 AN: 1261002 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 619526

African (AFR) AF: 0.00 AC: 0 AN: 25280

American (AMR) AF: 0.00 AC: 0 AN: 19104

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20386

East Asian (EAS) AF: 0.00 AC: 0 AN: 27626

South Asian (SAS) AF: 0.00 AC: 0 AN: 64696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31072

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4388

European-Non Finnish (NFE) AF: 0.00000197 AC: 2 AN: 1016722

Other (OTH) AF: 0.00 AC: 0 AN: 51728

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	9.5
DANN	Benign	0.97
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.0	T
PhyloP100		-2.6
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.069
Sift	Benign	0.39	T
Sift4G	Benign	0.69	T
Polyphen		0.0010	B
Vest4		0.046
MutPred		0.17		Loss of methylation at R4 (P = 0.102)
MVP		0.014
ClinPred		0.057	T
GERP RS		-0.68
PromoterAI		-0.031	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.020
gMVP		0.052
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs746807103; hg19: chr18-77724758;