rs2287863

Variant names:

• chr19-8514127-T-C
• rs2287863
• NM_001146175.2:c.-81A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZNF414	NM_001146175.2	c.-81A>G		5_prime_UTR_variant	Exon 1 of 8	ENST00000393927.9	NP_001139647.1
ZNF414	NM_032370.3	c.-81A>G		5_prime_UTR_variant	Exon 1 of 6		NP_115746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF414	ENST00000393927.9	c.-81A>G		5_prime_UTR_variant	Exon 1 of 8	1	NM_001146175.2	ENSP00000377504.3

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

African (AFR) AF: 0.296 AC: 7315 AN: 24706

American (AMR) AF: 0.168 AC: 2469 AN: 14716

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 3913 AN: 19286

East Asian (EAS) AF: 0.165 AC: 4521 AN: 27408

South Asian (SAS) AF: 0.138 AC: 8140 AN: 59124

European-Finnish (FIN) AF: 0.138 AC: 4495 AN: 32500

Middle Eastern (MID) AF: 0.176 AC: 845 AN: 4796

European-Non Finnish (NFE) AF: 0.168 AC: 167378 AN: 998534

Other (OTH) AF: 0.175 AC: 8812 AN: 50398

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

African (AFR) AF: 0.288 AC: 11929 AN: 41488

American (AMR) AF: 0.188 AC: 2872 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 714 AN: 3470

East Asian (EAS) AF: 0.166 AC: 855 AN: 5136

South Asian (SAS) AF: 0.133 AC: 639 AN: 4814

European-Finnish (FIN) AF: 0.133 AC: 1412 AN: 10606

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11722 AN: 67954

Other (OTH) AF: 0.205 AC: 433 AN: 2112

Alfa AF: 0.186 Hom.: 6781

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
PhyloP100		-0.34
PromoterAI		0.14	Neutral
Mutation Taster		=300/0	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: rs2287863; hg19: chr19-8579011;