NM_001098834.3:c.538+3852C>T

Variant names:

• chr7-151163159-G-A
• rs768403
• NM_001098834.3:c.538+3852C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098834.3(GBX1):​c.538+3852C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 151,462 control chromosomes in the GnomAD database, including 17,830 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 0.46 (17830 hom., cov: 30)
• Consequence: GBX1 NM_001098834.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.479
• Publications: 5 publications found

Genes affected

GBX1 (HGNC:4185): (gastrulation brain homeobox 1) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of nervous system development and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within adult walking behavior; neuron differentiation; and proprioception. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBX1	NM_001098834.3	c.538+3852C>T		intron_variant	Intron 1 of 1	ENST00000297537.5	NP_001092304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBX1	ENST00000297537.5	c.538+3852C>T		intron_variant	Intron 1 of 1	1	NM_001098834.3	ENSP00000297537.4
GBX1	ENST00000475831.1	n.311+3852C>T		intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70072 AN: 151344 Hom.: 17804 Cov.: 30

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.463 AC: 70144 AN: 151462 Hom.: 17830 Cov.: 30 AF XY: 0.461 AC XY: 34056 AN XY: 73946

African (AFR) AF: 0.680 AC: 28050 AN: 41254

American (AMR) AF: 0.393 AC: 5969 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1431 AN: 3468

East Asian (EAS) AF: 0.599 AC: 3082 AN: 5148

South Asian (SAS) AF: 0.288 AC: 1380 AN: 4788

European-Finnish (FIN) AF: 0.407 AC: 4246 AN: 10440

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24655 AN: 67872

Other (OTH) AF: 0.456 AC: 962 AN: 2108

Alfa AF: 0.450 Hom.: 2976

Bravo AF: 0.478

Asia WGS AF: 0.437 AC: 1522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.85
DANN	Benign	0.79
PhyloP100		-0.48
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: rs768403; hg19: chr7-150860246; COSMIC: COSV107392945;