rs612578

Positions:

• chr19-20661070-A-G

Variant summary

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

The NM_001076675.3(ZNF626):​c.3+374T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,144 control chromosomes in the GnomAD database, including 4,098 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 0.21 (4098 hom., cov: 33)
• Consequence: ZNF626 NM_001076675.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.638

Genes affected

ZNF626 (HGNC:30461): (zinc finger protein 626) 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]

ENSG00000269110 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF626	NM_001076675.3	c.3+374T>C		intron_variant		ENST00000601440.6	NP_001070143.1
ZNF626	NM_145297.4	c.3+374T>C		intron_variant			NP_660340.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF626	ENST00000601440.6	c.3+374T>C		intron_variant		4	NM_001076675.3	ENSP00000469958.1
ZNF626	ENST00000291750.6	c.3+374T>C		intron_variant		1		ENSP00000291750.6
ZNF626	ENST00000595405.1	c.-3+374T>C		intron_variant		3		ENSP00000469566.1
ENSG00000269110	ENST00000595094.1	n.140+374T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32682 AN: 152024 Hom.: 4094 Cov.: 33

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.215 AC: 32709 AN: 152144 Hom.: 4098 Cov.: 33 AF XY: 0.217 AC XY: 16117 AN XY: 74368

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.224

Alfa AF: 0.246 Hom.: 5747

Bravo AF: 0.221

Asia WGS AF: 0.288 AC: 1001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.0
DANN	Benign	0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs612578; hg19: chr19-20843876;