rs10503835

chr8-28965578-A-G

Variant summary

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

The NM_001135726.3(HMBOX1):c.23+1688A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,142 control chromosomes in the GnomAD database, including 3,500 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 0.21 (3500 hom., cov: 32)
• Consequence: HMBOX1 NM_001135726.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.419

Genes affected

HMBOX1 (HGNC:26137): (homeobox containing 1) Enables double-stranded telomeric DNA binding activity; identical protein binding activity; and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II; positive regulation of telomerase activity; and positive regulation of telomere maintenance via telomerase. Located in several cellular components, including centrosome; chromosome, telomeric region; and nuclear body. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMBOX1	NM_001135726.3	c.23+1688A>G		intron_variant		ENST00000287701.15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMBOX1	ENST00000287701.15	c.23+1688A>G		intron_variant		1	NM_001135726.3	P4

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32107 AN: 152024 Hom.: 3505 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.211 AC: 32109 AN: 152142 Hom.: 3500 Cov.: 32 AF XY: 0.211 AC XY: 15675 AN XY: 74380

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.210

Alfa AF: 0.229 Hom.: 2449

Bravo AF: 0.204

Asia WGS AF: 0.222 AC: 774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.9
Dann	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10503835; hg19: chr8-28823095;