chr16-180841-C-T

Variant names:

• chr16-180841-C-T
• rs747380563
• NM_005331.5:c.271C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005331.5(HBQ1):​c.271C>T​(p.Gln91*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,391,502 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000014 (1 hom.)
• Consequence: HBQ1 NM_005331.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302
• Publications: 1 publications found

Genes affected

HBQ1 (HGNC:4833): (hemoglobin subunit theta 1) Theta-globin mRNA is found in human fetal erythroid tissue but not in adult erythroid or other nonerythroid tissue. The theta-1 gene may be expressed very early in embryonic life, perhaps sometime before 5 weeks. Theta-1 is a member of the human alpha-globin gene cluster that involves five functional genes and two pseudogenes. The order of genes is: 5' - zeta - pseudozeta - mu - pseudoalpha-2 -pseudoalpha-1 - alpha-2 - alpha-1 - theta-1 - 3'. Research supports a transcriptionally active role for the gene and a functional role for the peptide in specific cells, possibly those of early erythroid tissue. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005331.5. 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
	HBQ1	NM_005331.5	MANE Select	c.271C>T	p.Gln91*	stop_gained	Exon 2 of 3	NP_005322.1	P09105

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBQ1	ENST00000199708.3	TSL:1 MANE Select	c.271C>T	p.Gln91*	stop_gained	Exon 2 of 3	ENSP00000199708.2	P09105

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000418 AC: 6 AN: 143682 AF XY: 0.0000762

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 19 AN: 1391502 Hom.: 1 Cov.: 34 AF XY: 0.0000247 AC XY: 17 AN XY: 687190

African (AFR) AF: 0.00 AC: 0 AN: 31716

American (AMR) AF: 0.00 AC: 0 AN: 36590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 36034

South Asian (SAS) AF: 0.000187 AC: 15 AN: 80114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37796

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080456

Other (OTH) AF: 0.0000690 AC: 4 AN: 57940

GnomAD4 genome Cov.: 33

Alfa AF: 0.000987 Hom.: 3

Bravo AF: 0.00000378

ExAC AF: 0.0000274 AC: 3

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	27
DANN	Benign	0.87
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.086	N
PhyloP100		0.30
Vest4		0.093
GERP RS		-2.8
PromoterAI		-0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=157/43	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs747380563; hg19: chr16-230840;