rs11993726

Variant names:

• chr8-29019345-A-T
• rs11993726
• NM_001135726.3:c.851+432A>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.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
• Publications: 1 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0668 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMBOX1	NM_001135726.3	MANE Select	c.851+432A>T		intron	N/A	NP_001129198.1	Q6NT76-1
	HMBOX1	NM_001324383.2		c.851+432A>T		intron	N/A	NP_001311312.1
	HMBOX1	NM_001324384.1		c.851+432A>T		intron	N/A	NP_001311313.1	Q6NT76

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMBOX1	ENST00000287701.15	TSL:1 MANE Select	c.851+432A>T		intron	N/A	ENSP00000287701.10	Q6NT76-1
	HMBOX1	ENST00000397358.7	TSL:1	c.851+432A>T		intron	N/A	ENSP00000380516.3	Q6NT76-1
	HMBOX1	ENST00000523613.5	TSL:1	c.851+432A>T		intron	N/A	ENSP00000452827.1	H0YKJ1

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

African (AFR) AF: 0.0689 AC: 2858 AN: 41496

American (AMR) AF: 0.00935 AC: 143 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10564

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 67972

Other (OTH) AF: 0.0185 AC: 39 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.56
DANN	Benign	0.80
PhyloP100		-0.28
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: rs11993726; hg19: chr8-28876862;