rs2287863

Positions:

• chr19-8514127-T-C

Variant summary

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

The NM_001146175.2(ZNF414):​c.-81A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,383,552 control chromosomes in the GnomAD database, including 21,529 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 0.20 (3426 hom., cov: 33)
  • Exomes 𝑓: 0.17 (18103 hom.)
• Consequence: ZNF414 NM_001146175.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339

Genes affected

ZNF414 (HGNC:20630): (zinc finger protein 414) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF414	NM_001146175.2	c.-81A>G		5_prime_UTR_variant	1/8	ENST00000393927.9	NP_001139647.1
ZNF414	NM_032370.3	c.-81A>G		5_prime_UTR_variant	1/6		NP_115746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF414	ENST00000393927.9	c.-81A>G		5_prime_UTR_variant	1/8	1	NM_001146175.2	ENSP00000377504	P1
ZNF414	ENST00000255616.8	c.-81A>G		5_prime_UTR_variant	1/6	1		ENSP00000255616
ZNF414	ENST00000600906.1	n.38A>G		non_coding_transcript_exon_variant	1/2	2
ZNF414	ENST00000599379.1	c.-81A>G		5_prime_UTR_variant, NMD_transcript_variant	1/4	2		ENSP00000472741

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30761 AN: 151970 Hom.: 3420 Cov.: 33

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.169 AC: 207888 AN: 1231468 Hom.: 18103 Cov.: 28 AF XY: 0.168 AC XY: 101112 AN XY: 601228

Gnomad4 AFR exome AF: 0.296

Gnomad4 AMR exome AF: 0.168

Gnomad4 ASJ exome AF: 0.203

Gnomad4 EAS exome AF: 0.165

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.175

GnomAD4 genome AF: 0.203 AC: 30803 AN: 152084 Hom.: 3426 Cov.: 33 AF XY: 0.201 AC XY: 14913 AN XY: 74360

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.205

Alfa AF: 0.178 Hom.: 3927

Bravo AF: 0.211

Asia WGS AF: 0.171 AC: 594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.5
DANN	Benign	0.52

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: rs2287863; hg19: chr19-8579011;