14-23549129-T-C

Variant names:

• chr14-23549129-T-C
• rs222682
• NM_033400.3:c.-50+2214A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033400.3(ZFHX2):​c.-50+2214A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 151,944 control chromosomes in the GnomAD database, including 34,109 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 0.65 (34109 hom., cov: 30)
• Consequence: ZFHX2 NM_033400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

Genes affected

ZFHX2 (HGNC:20152): (zinc finger homeobox 2) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in regulation of sensory perception of pain. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZFHX2-AS1 (HGNC:52658): (ZFHX2 antisense RNA 1)

THTPA (HGNC:18987): (thiamine triphosphatase) This gene encodes an enzyme which catalyzes the biosynthesis of thiamine disphophate (vitamin B1) by hydrolysis of thiamine triphosphate. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFHX2	NM_033400.3	c.-50+2214A>G		intron_variant	Intron 1 of 9	ENST00000419474.5	NP_207646.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFHX2	ENST00000419474.5	c.-50+2214A>G		intron_variant	Intron 1 of 9	5	NM_033400.3	ENSP00000413418.2
ZFHX2	ENST00000412565.2	c.-50+6594A>G		intron_variant	Intron 1 of 1	2		ENSP00000409464.2
ZFHX2-AS1	ENST00000553985.1	n.239-9566T>C		intron_variant	Intron 2 of 2	2
ZFHX2-AS1	ENST00000556354.5	n.466-9566T>C		intron_variant	Intron 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.652 AC: 98996 AN: 151824 Hom.: 34102 Cov.: 30

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.745

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.652 AC: 99029 AN: 151944 Hom.: 34109 Cov.: 30 AF XY: 0.649 AC XY: 48212 AN XY: 74258

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.646

Gnomad4 ASJ AF: 0.869

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.715

Gnomad4 NFE AF: 0.774

Gnomad4 OTH AF: 0.702

Alfa AF: 0.757 Hom.: 61566

Bravo AF: 0.637

Asia WGS AF: 0.661 AC: 2297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.85
DANN	Benign	0.88

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: rs222682; hg19: chr14-24018338;