rs11993726

chr8-29019345-A-T

Variant summary

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

The NM_001135726.3(HMBOX1):c.851+432A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0202 in 152,110 control chromosomes in the GnomAD database, including 91 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 0.020 (91 hom., cov: 32)
• Consequence: HMBOX1 NM_001135726.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMBOX1	NM_001135726.3	c.851+432A>T		intron_variant		ENST00000287701.15
LOC105379346	XR_001745858.2	n.7248-4223T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMBOX1	ENST00000287701.15	c.851+432A>T		intron_variant		1	NM_001135726.3	P4

Frequencies

GnomAD3 genomes AF: 0.0202 AC: 3075 AN: 151992 Hom.: 91 Cov.: 32

Gnomad AFR AF: 0.0691

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00937

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.0187

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

GnomAD4 genome AF: 0.0202 AC: 3075 AN: 152110 Hom.: 91 Cov.: 32 AF XY: 0.0193 AC XY: 1435 AN XY: 74376

Gnomad4 AFR AF: 0.0689

Gnomad4 AMR AF: 0.00935

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000441

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.0129 Hom.: 11

Bravo AF: 0.0230

Asia WGS AF: 0.00492 AC: 17 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.56
Dann	Benign	0.80

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: rs11993726; hg19: chr8-28876862;