rs1390401

Variant names:

• chr1-227610249-A-G
• rs1390401
• NM_001367909.1:c.-163-36295A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 38 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZNF678	NM_001367909.1	c.-163-36295A>G		intron_variant	Intron 1 of 3	ENST00000343776.10	NP_001354838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF678	ENST00000343776.10	c.-163-36295A>G		intron_variant	Intron 1 of 3	1	NM_001367909.1	ENSP00000344828.4
ZNF678	ENST00000608949.5	c.-164+27643A>G		intron_variant	Intron 2 of 5	1		ENSP00000477097.1
ZNF678	ENST00000440339.1	c.123+27643A>G		intron_variant	Intron 2 of 3	2		ENSP00000394651.1
ZNF678	ENST00000465266.1	n.267+27643A>G		intron_variant	Intron 2 of 4	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

African (AFR) AF: 0.398 AC: 16498 AN: 41466

American (AMR) AF: 0.137 AC: 2092 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 395 AN: 3472

East Asian (EAS) AF: 0.0926 AC: 480 AN: 5186

South Asian (SAS) AF: 0.179 AC: 865 AN: 4830

European-Finnish (FIN) AF: 0.212 AC: 2237 AN: 10568

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12610 AN: 67982

Other (OTH) AF: 0.199 AC: 420 AN: 2110

Alfa AF: 0.202 Hom.: 7540

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
PhyloP100		0.21
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: rs1390401; hg19: chr1-227797950;