rs1128163

Positions:

• chr3-121631726-A-G
• chr3-121631726-A-T

Variant summary

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

The NM_005335.6(HCLS1):​c.*120T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,053,022 control chromosomes in the GnomAD database, including 31,156 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 0.23 (4169 hom., cov: 31)
  • Exomes 𝑓: 0.24 (26987 hom.)
• Consequence: HCLS1 NM_005335.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HCLS1	NM_005335.6	c.*120T>C		3_prime_UTR_variant	14/14	ENST00000314583.8
HCLS1	NM_001292041.2	c.*120T>C		3_prime_UTR_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCLS1	ENST00000314583.8	c.*120T>C		3_prime_UTR_variant	14/14	1	NM_005335.6	P1
HCLS1	ENST00000428394.6	c.*120T>C		3_prime_UTR_variant	13/13	2
HCLS1	ENST00000473883.5	n.2384T>C		non_coding_transcript_exon_variant	9/9	2

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34303 AN: 151862 Hom.: 4173 Cov.: 31

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.260

GnomAD4 exome AF: 0.239 AC: 215004 AN: 901042 Hom.: 26987 Cov.: 12 AF XY: 0.239 AC XY: 108818 AN XY: 455572

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.163

Gnomad4 ASJ exome AF: 0.303

Gnomad4 EAS exome AF: 0.394

Gnomad4 SAS exome AF: 0.231

Gnomad4 FIN exome AF: 0.213

Gnomad4 NFE exome AF: 0.235

Gnomad4 OTH exome AF: 0.261

GnomAD4 genome AF: 0.226 AC: 34300 AN: 151980 Hom.: 4169 Cov.: 31 AF XY: 0.224 AC XY: 16609 AN XY: 74292

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.258

Alfa AF: 0.233 Hom.: 1675

Bravo AF: 0.225

Asia WGS AF: 0.288 AC: 1000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.0
DANN	Benign	0.63

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: rs1128163; hg19: chr3-121350573; COSMIC: COSV57526052; COSMIC: COSV57526052;