7-107169848-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_012257.4(HBP1):c.-16+663G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 984,984 control chromosomes in the GnomAD database, including 18,734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1943 hom., cov: 31)
  • Exomes 𝑓: 0.20 (16791 hom.)
• Consequence: HBP1 NM_012257.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.12

Genes affected

HBP1 (HGNC:23200): (HMG-box transcription factor 1) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of lipid transport; negative regulation of reactive oxygen species biosynthetic process; and negative regulation of transcription by RNA polymerase II. Located in nuclear speck. Biomarker of osteoarthritis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 7-107169848-G-C is Benign according to our data. Variant chr7-107169848-G-C is described in ClinVar as [Benign]. Clinvar id is 1277741.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HBP1	NM_012257.4	c.-16+663G>C		intron_variant		ENST00000222574.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HBP1	ENST00000222574.9	c.-16+663G>C		intron_variant		1	NM_012257.4	P1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21702 AN: 151880 Hom.: 1945 Cov.: 31

Gnomad AFR AF: 0.0390

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.153

GnomAD4 exome AF: 0.200 AC: 166296 AN: 832986 Hom.: 16791 Cov.: 31 AF XY: 0.201 AC XY: 77157 AN XY: 384708

Gnomad4 AFR exome AF: 0.0262

Gnomad4 AMR exome AF: 0.142

Gnomad4 ASJ exome AF: 0.242

Gnomad4 EAS exome AF: 0.140

Gnomad4 SAS exome AF: 0.197

Gnomad4 FIN exome AF: 0.191

Gnomad4 NFE exome AF: 0.204

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome AF: 0.143 AC: 21696 AN: 151998 Hom.: 1943 Cov.: 31 AF XY: 0.141 AC XY: 10467 AN XY: 74288

Gnomad4 AFR AF: 0.0391

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.152

Alfa AF: 0.0731 Hom.: 103

Bravo AF: 0.141

Asia WGS AF: 0.166 AC: 576 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 18, 2020

This variant is associated with the following publications: (PMID: 31164647) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
Cadd	Benign	18
Dann	Benign	0.92
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		4.1

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: rs4730222; hg19: chr7-106810293;