rs10088428

Variant names:

• chr8-29052006-C-T
• rs10088428
• NM_001135726.3:c.*851C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 29 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HMBOX1	NM_001135726.3	c.*851C>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000287701.15	NP_001129198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMBOX1	ENST00000287701.15	c.*851C>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_001135726.3	ENSP00000287701.10

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

African (AFR) AF: 0.396 AC: 111 AN: 280

American (AMR) AF: 0.158 AC: 150 AN: 950

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 100 AN: 282

East Asian (EAS) AF: 0.0435 AC: 29 AN: 666

South Asian (SAS) AF: 0.246 AC: 120 AN: 488

European-Finnish (FIN) AF: 0.362 AC: 58 AN: 160

Middle Eastern (MID) AF: 0.308 AC: 8 AN: 26

European-Non Finnish (NFE) AF: 0.278 AC: 1504 AN: 5408

Other (OTH) AF: 0.249 AC: 113 AN: 454

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

African (AFR) AF: 0.348 AC: 14339 AN: 41218

American (AMR) AF: 0.196 AC: 2984 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 982 AN: 3468

East Asian (EAS) AF: 0.0495 AC: 255 AN: 5154

South Asian (SAS) AF: 0.196 AC: 941 AN: 4794

European-Finnish (FIN) AF: 0.298 AC: 3105 AN: 10414

Middle Eastern (MID) AF: 0.324 AC: 94 AN: 290

European-Non Finnish (NFE) AF: 0.264 AC: 17924 AN: 67948

Other (OTH) AF: 0.278 AC: 584 AN: 2102

Alfa AF: 0.263 Hom.: 14862

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
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10088428; hg19: chr8-28909523;