19-21521677-T-G

Variant names:

• chr19-21521677-T-G
• rs1879234
• NM_001001415.4:c.4-7981T>G

Variant summary

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

The NM_001001415.4(ZNF429):​c.4-7981T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,730 control chromosomes in the GnomAD database, including 50,334 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 0.81 (50111 hom., cov: 32)
  • Exomes 𝑓: 0.88 (223 hom.)
• Consequence: ZNF429 NM_001001415.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 5 publications found

Genes affected

ZNF429 (HGNC:20817): (zinc finger protein 429) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

BNIP3P26 (HGNC:49706): (BCL2 interacting protein 3 pseudogene 26)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001415.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF429	NM_001001415.4	MANE Select	c.4-7981T>G		intron	N/A	NP_001001415.2
	ZNF429	NM_001346912.2		c.17-8000T>G		intron	N/A	NP_001333841.1
	ZNF429	NM_001346913.2		c.-93-7981T>G		intron	N/A	NP_001333842.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF429	ENST00000358491.9	TSL:3 MANE Select	c.4-7981T>G		intron	N/A	ENSP00000351280.3
	ZNF429	ENST00000597078.5	TSL:1	c.4-7981T>G		intron	N/A	ENSP00000470300.1
	BNIP3P26	ENST00000600827.1	TSL:6	n.220A>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122577 AN: 152040 Hom.: 50071 Cov.: 32

Gnomad AFR AF: 0.944

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.799

GnomAD4 exome AF: 0.879 AC: 503 AN: 572 Hom.: 223 Cov.: 0 AF XY: 0.870 AC XY: 261 AN XY: 300

African (AFR) AF: 1.00 AC: 18 AN: 18

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.929 AC: 13 AN: 14

European-Finnish (FIN) AF: 0.917 AC: 11 AN: 12

Middle Eastern (MID) AF: 0.894 AC: 345 AN: 386

European-Non Finnish (NFE) AF: 0.790 AC: 79 AN: 100

Other (OTH) AF: 0.895 AC: 34 AN: 38

GnomAD4 genome AF: 0.806 AC: 122669 AN: 152158 Hom.: 50111 Cov.: 32 AF XY: 0.805 AC XY: 59868 AN XY: 74370

African (AFR) AF: 0.944 AC: 39217 AN: 41526

American (AMR) AF: 0.737 AC: 11269 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.834 AC: 2894 AN: 3472

East Asian (EAS) AF: 0.715 AC: 3693 AN: 5162

South Asian (SAS) AF: 0.807 AC: 3894 AN: 4826

European-Finnish (FIN) AF: 0.754 AC: 7966 AN: 10564

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51137 AN: 68004

Other (OTH) AF: 0.794 AC: 1676 AN: 2110

Alfa AF: 0.751 Hom.: 2852

Bravo AF: 0.809

Asia WGS AF: 0.739 AC: 2572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.29
PhyloP100		-1.4
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: rs1879234; hg19: chr19-21704479;