chr3-121652216-T-C

Position:

• chr3-121652216-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005335.6(HCLS1):​c.159-4768A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 152,086 control chromosomes in the GnomAD database, including 37,665 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 0.70 (37665 hom., cov: 32)
• Consequence: HCLS1 NM_005335.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

Genes affected

HCLS1 (HGNC:4844): (hematopoietic cell-specific Lyn substrate 1) Enables RNA polymerase II-specific DNA-binding transcription factor binding activity and protein kinase binding activity. Involved in several processes, including positive regulation of intracellular signal transduction; positive regulation of protein phosphorylation; and regulation of transcription, DNA-templated. Located in cytosol; nucleus; and plasma membrane. Part of transcription regulator complex. [provided by Alliance of Genome Resources, Apr 2022]

HCLS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCLS1	NM_005335.6	c.159-4768A>G		intron_variant		ENST00000314583.8	NP_005326.3
HCLS1	NM_001292041.2	c.159-4768A>G		intron_variant			NP_001278970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HCLS1	ENST00000314583.8	c.159-4768A>G		intron_variant		1	NM_005335.6	ENSP00000320176.3

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105869 AN: 151968 Hom.: 37655 Cov.: 32

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.701

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.696 AC: 105911 AN: 152086 Hom.: 37665 Cov.: 32 AF XY: 0.689 AC XY: 51244 AN XY: 74336

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.855

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.743

Gnomad4 NFE AF: 0.764

Gnomad4 OTH AF: 0.702

Alfa AF: 0.705 Hom.: 6243

Bravo AF: 0.682

Asia WGS AF: 0.711 AC: 2471 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.47
DANN	Benign	0.67

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

Other links and lift over

dbSNP: rs9864907; hg19: chr3-121371063;