8-28933642-G-C

Variant names:

• chr8-28933642-G-C
• rs2221894
• NM_001135726.3:c.-57-30169G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001135726.3(HMBOX1):​c.-57-30169G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: HMBOX1 NM_001135726.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431
• Publications: 18 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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.-57-30169G>C		intron	N/A	NP_001129198.1	Q6NT76-1
	HMBOX1	NM_001324383.2		c.-57-30169G>C		intron	N/A	NP_001311312.1
	HMBOX1	NM_001324384.1		c.-57-30169G>C		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.-57-30169G>C		intron	N/A	ENSP00000287701.10	Q6NT76-1
	HMBOX1	ENST00000397358.7	TSL:1	c.-57-30169G>C		intron	N/A	ENSP00000380516.3	Q6NT76-1
	HMBOX1	ENST00000523613.5	TSL:1	c.-57-30169G>C		intron	N/A	ENSP00000452827.1	H0YKJ1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.92
DANN	Benign	0.37
PhyloP100		0.43

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: rs2221894; hg19: chr8-28791159;