rs1390401

Positions:

• chr1-227610249-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.-163-36295A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,106 control chromosomes in the GnomAD database, including 5,112 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 (5112 hom., cov: 32)
• Consequence: ZNF678 NM_001367909.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF678	NM_001367909.1	c.-163-36295A>G		intron_variant		ENST00000343776.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF678	ENST00000343776.10	c.-163-36295A>G		intron_variant		1	NM_001367909.1	P1
ZNF678	ENST00000608949.5	c.-164+27643A>G		intron_variant		1
ZNF678	ENST00000440339.1	c.123+27643A>G		intron_variant		2
ZNF678	ENST00000465266.1	n.267+27643A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35731 AN: 151988 Hom.: 5104 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.0933

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.235 AC: 35752 AN: 152106 Hom.: 5112 Cov.: 32 AF XY: 0.234 AC XY: 17403 AN XY: 74376

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.0926

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.199

Alfa AF: 0.209 Hom.: 1612

Bravo AF: 0.235

Asia WGS AF: 0.124 AC: 433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.4
DANN	Benign	0.27

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: rs1390401; hg19: chr1-227797950;