1-227584695-A-G

Variant names:

• chr1-227584695-A-G
• rs3942992
• NM_001367909.1:c.-164+20971A>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.-164+20971A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 152,190 control chromosomes in the GnomAD database, including 45,459 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 0.77 (45459 hom., cov: 33)
• Consequence: ZNF678 NM_001367909.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792
• Publications: 9 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF678	NM_001367909.1	c.-164+20971A>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.-164+20971A>G		intron_variant	Intron 1 of 3	1	NM_001367909.1	ENSP00000344828.4
ZNF678	ENST00000608949.5	c.-164+2089A>G		intron_variant	Intron 2 of 5	1		ENSP00000477097.1
ZNF678	ENST00000440339.1	c.123+2089A>G		intron_variant	Intron 2 of 3	2		ENSP00000394651.1
ZNF678	ENST00000465266.1	n.267+2089A>G		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116366 AN: 152072 Hom.: 45413 Cov.: 33

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.868

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.798

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

GnomAD4 genome AF: 0.765 AC: 116463 AN: 152190 Hom.: 45459 Cov.: 33 AF XY: 0.766 AC XY: 57011 AN XY: 74406

African (AFR) AF: 0.603 AC: 25029 AN: 41478

American (AMR) AF: 0.863 AC: 13205 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.886 AC: 3077 AN: 3472

East Asian (EAS) AF: 0.907 AC: 4702 AN: 5182

South Asian (SAS) AF: 0.822 AC: 3963 AN: 4824

European-Finnish (FIN) AF: 0.788 AC: 8341 AN: 10590

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55405 AN: 68024

Other (OTH) AF: 0.800 AC: 1690 AN: 2112

Alfa AF: 0.808 Hom.: 79850

Bravo AF: 0.765

Asia WGS AF: 0.875 AC: 3044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.7
DANN	Benign	0.65
PhyloP100		-0.79
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: rs3942992; hg19: chr1-227772396;