8-29027953-T-C

Variant names:

• chr8-29027953-T-C
• rs10503836
• NM_001135726.3:c.851+9040T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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]

LOC105379346 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135726.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMBOX1	NM_001135726.3	MANE Select	c.851+9040T>C		intron	N/A	NP_001129198.1
	HMBOX1	NM_001324383.2		c.851+9040T>C		intron	N/A	NP_001311312.1
	HMBOX1	NM_001324384.1		c.851+9040T>C		intron	N/A	NP_001311313.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMBOX1	ENST00000287701.15	TSL:1 MANE Select	c.851+9040T>C		intron	N/A	ENSP00000287701.10
	HMBOX1	ENST00000397358.7	TSL:1	c.851+9040T>C		intron	N/A	ENSP00000380516.3
	HMBOX1	ENST00000523613.5	TSL:1	c.851+9040T>C		intron	N/A	ENSP00000452827.1

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

African (AFR) AF: 0.248 AC: 10292 AN: 41500

American (AMR) AF: 0.515 AC: 7861 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1574 AN: 3468

East Asian (EAS) AF: 0.226 AC: 1171 AN: 5180

South Asian (SAS) AF: 0.367 AC: 1770 AN: 4828

European-Finnish (FIN) AF: 0.493 AC: 5196 AN: 10550

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36204 AN: 67938

Other (OTH) AF: 0.442 AC: 934 AN: 2114

Alfa AF: 0.473 Hom.: 3558

Bravo AF: 0.424

Asia WGS AF: 0.296 AC: 1030 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.1
DANN	Benign	0.72
PhyloP100		2.8
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: rs10503836; hg19: chr8-28885470;