8-29052006-C-T

Position:

• chr8-29052006-C-T

Variant summary

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

The NM_001135726.3(HMBOX1):​c.*851C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 160,236 control chromosomes in the GnomAD database, including 6,344 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 0.27 (5989 hom., cov: 31)
  • Exomes 𝑓: 0.25 (355 hom.)
• Consequence: HMBOX1 NM_001135726.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.564

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMBOX1	NM_001135726.3	c.*851C>T		3_prime_UTR_variant	10/10	ENST00000287701.15	NP_001129198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMBOX1	ENST00000287701.15	c.*851C>T		3_prime_UTR_variant	10/10	1	NM_001135726.3	ENSP00000287701	P4
HMBOX1	ENST00000397358.7	c.*851C>T		3_prime_UTR_variant	11/11	1		ENSP00000380516	P4
HMBOX1	ENST00000522468.1	c.*8+843C>T		intron_variant, NMD_transcript_variant		3		ENSP00000429854

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41470 AN: 151426 Hom.: 5975 Cov.: 31

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.0496

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.311

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.271

GnomAD4 exome AF: 0.252 AC: 2193 AN: 8714 Hom.: 355 Cov.: 0 AF XY: 0.250 AC XY: 1133 AN XY: 4538

Gnomad4 AFR exome AF: 0.396

Gnomad4 AMR exome AF: 0.158

Gnomad4 ASJ exome AF: 0.355

Gnomad4 EAS exome AF: 0.0435

Gnomad4 SAS exome AF: 0.246

Gnomad4 FIN exome AF: 0.362

Gnomad4 NFE exome AF: 0.278

Gnomad4 OTH exome AF: 0.249

GnomAD4 genome AF: 0.274 AC: 41519 AN: 151522 Hom.: 5989 Cov.: 31 AF XY: 0.269 AC XY: 19877 AN XY: 73968

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.0495

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.278

Alfa AF: 0.259 Hom.: 4823

Bravo AF: 0.269

Asia WGS AF: 0.151 AC: 527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.7
DANN	Benign	0.78

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: rs10088428; hg19: chr8-28909523;