19-56464017-G-T

Variant names:

• chr19-56464017-G-T
• rs4801163
• NM_001321356.2:c.-59-1588C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321356.2(ZNF667):​c.-59-1588C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,002 control chromosomes in the GnomAD database, including 11,844 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 0.39 (11844 hom., cov: 32)
• Consequence: ZNF667 NM_001321356.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.596
• Publications: 5 publications found

Genes affected

ZNF667 (HGNC:28854): (zinc finger protein 667) Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. 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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321356.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF667	NM_001321356.2	MANE Select	c.-59-1588C>A		intron	N/A	NP_001308285.1
	ZNF667	NM_022103.4		c.-59-1588C>A		intron	N/A	NP_071386.3
	ZNF667	NM_001321355.2		c.-331-1588C>A		intron	N/A	NP_001308284.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF667	ENST00000504904.8	TSL:2 MANE Select	c.-59-1588C>A		intron	N/A	ENSP00000439402.1
	ZNF667	ENST00000292069.10	TSL:1	c.-59-1588C>A		intron	N/A	ENSP00000292069.5
	ZNF667	ENST00000587555.5	TSL:4	c.-59-1588C>A		intron	N/A	ENSP00000468466.1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59118 AN: 151884 Hom.: 11840 Cov.: 32

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.389 AC: 59150 AN: 152002 Hom.: 11844 Cov.: 32 AF XY: 0.385 AC XY: 28596 AN XY: 74310

African (AFR) AF: 0.367 AC: 15215 AN: 41412

American (AMR) AF: 0.353 AC: 5399 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1840 AN: 3470

East Asian (EAS) AF: 0.117 AC: 608 AN: 5176

South Asian (SAS) AF: 0.370 AC: 1789 AN: 4830

European-Finnish (FIN) AF: 0.340 AC: 3583 AN: 10538

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29428 AN: 67976

Other (OTH) AF: 0.407 AC: 860 AN: 2112

Alfa AF: 0.425 Hom.: 7356

Bravo AF: 0.388

Asia WGS AF: 0.251 AC: 878 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.89
DANN	Benign	0.78
PhyloP100		-0.60
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: rs4801163; hg19: chr19-56975386;