rs10503836

chr8-29027953-T-C

Variant summary

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

The NM_001135726.3(HMBOX1):c.851+9040T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 152,044 control chromosomes in the GnomAD database, including 15,450 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 0.43 (15450 hom., cov: 32)
• Consequence: HMBOX1 NM_001135726.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.80

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]

LOC105379346 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMBOX1	NM_001135726.3	c.851+9040T>C		intron_variant		ENST00000287701.15
LOC105379346	XR_001745858.2	n.7247+3173A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMBOX1	ENST00000287701.15	c.851+9040T>C		intron_variant		1	NM_001135726.3	P4

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65417 AN: 151926 Hom.: 15452 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.430 AC: 65423 AN: 152044 Hom.: 15450 Cov.: 32 AF XY: 0.428 AC XY: 31800 AN XY: 74322

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.442

Alfa AF: 0.478 Hom.: 3529

Bravo AF: 0.424

Asia WGS AF: 0.296 AC: 1030 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	8.1
Dann	Benign	0.72

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: rs10503836; hg19: chr8-28885470;