rs1045407

Positions:

• chr1-227659532-A-G

Variant summary

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

The NM_001367909.1(ZNF678):​c.*3704A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,096 control chromosomes in the GnomAD database, including 5,428 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 0.24 (5428 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF678 NM_001367909.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31

Genes affected

ZNF678 (HGNC:28652): (zinc finger protein 678) 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

VN1R15P (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF678	NM_001367909.1	c.*3704A>G		3_prime_UTR_variant	4/4	ENST00000343776.10	NP_001354838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF678	ENST00000343776.10	c.*3704A>G		3_prime_UTR_variant	4/4	1	NM_001367909.1	ENSP00000344828.4
ZNF678	ENST00000397097.4	c.*3704A>G		3_prime_UTR_variant	2/2	1		ENSP00000440403.2
ZNF678	ENST00000608949.5	c.226+5056A>G		intron_variant		1		ENSP00000477097.1

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37048 AN: 151978 Hom.: 5418 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0924

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.213

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.244 AC: 37076 AN: 152096 Hom.: 5428 Cov.: 32 AF XY: 0.242 AC XY: 17983 AN XY: 74378

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.0916

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.211

Alfa AF: 0.229 Hom.: 883

Bravo AF: 0.243

Asia WGS AF: 0.127 AC: 443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.5
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1045407; hg19: chr1-227847233;