rs6470120

Variant names:

• chr8-122868979-G-A
• rs6470120
• NM_014943.5:c.-220+5440G>A

Variant summary

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

The NM_014943.5(ZHX2):​c.-220+5440G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,146 control chromosomes in the GnomAD database, including 11,900 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 0.38 (11900 hom., cov: 32)
• Consequence: ZHX2 NM_014943.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970
• Publications: 5 publications found

Genes affected

ZHX2 (HGNC:18513): (zinc fingers and homeoboxes 2) The members of the zinc fingers and homeoboxes gene family are nuclear homodimeric transcriptional repressors that interact with the A subunit of nuclear factor-Y (NF-YA) and contain two C2H2-type zinc fingers and five homeobox DNA-binding domains. This gene encodes member 2 of this gene family. In addition to forming homodimers, this protein heterodimerizes with member 1 of the zinc fingers and homeoboxes family. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZHX2	NM_014943.5	c.-220+5440G>A		intron_variant	Intron 2 of 3	ENST00000314393.6	NP_055758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZHX2	ENST00000314393.6	c.-220+5440G>A		intron_variant	Intron 2 of 3	1	NM_014943.5	ENSP00000314709.4
ZHX2	ENST00000534247.1	c.-220+5440G>A		intron_variant	Intron 1 of 1	3		ENSP00000452720.1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58418 AN: 152028 Hom.: 11883 Cov.: 32

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.384 AC: 58481 AN: 152146 Hom.: 11900 Cov.: 32 AF XY: 0.384 AC XY: 28595 AN XY: 74388

African (AFR) AF: 0.526 AC: 21848 AN: 41518

American (AMR) AF: 0.296 AC: 4526 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1013 AN: 3468

East Asian (EAS) AF: 0.365 AC: 1886 AN: 5164

South Asian (SAS) AF: 0.334 AC: 1611 AN: 4824

European-Finnish (FIN) AF: 0.383 AC: 4049 AN: 10584

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22453 AN: 67984

Other (OTH) AF: 0.348 AC: 735 AN: 2112

Alfa AF: 0.344 Hom.: 29689

Bravo AF: 0.386

Asia WGS AF: 0.351 AC: 1223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.55
PhyloP100		0.097
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: rs6470120; hg19: chr8-123881218;