19-52846597-C-T

Position:

• chr19-52846597-C-T

Variant summary

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

The NM_001008801.2(ZNF468):​c.142+2490G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 156,010 control chromosomes in the GnomAD database, including 9,994 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 0.32 (9994 hom., cov: 33)
  • Exomes 𝑓: 0.016 (0 hom.)
• Consequence: ZNF468 NM_001008801.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.624

Genes affected

ZNF468 (HGNC:33105): (zinc finger protein 468) 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 by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF28 (HGNC:13073): (zinc finger protein 28) 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 by RNA polymerase II. Predicted to be active 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 (MetaRNN=1.8554392E-5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF468	NM_001008801.2	c.142+2490G>A		intron_variant		ENST00000595646.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF468	ENST00000595646.6	c.142+2490G>A		intron_variant		1	NM_001008801.2	P1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48657 AN: 152008 Hom.: 9999 Cov.: 33

Gnomad AFR AF: 0.0911

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.0487

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.333

GnomAD3 exomes AF: 0.591 AC: 13 AN: 22 Hom.: 5 AF XY: 0.750 AC XY: 3 AN XY: 4

Gnomad AFR exome AF: 0.00

Gnomad FIN exome AF: 0.500

Gnomad NFE exome AF: 0.667

GnomAD4 exome AF: 0.0157 AC: 61 AN: 3888 Hom.: 0 Cov.: 0 AF XY: 0.0164 AC XY: 31 AN XY: 1890

Gnomad4 AFR exome AF: 0.00420

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0141

Gnomad4 NFE exome AF: 0.0171

Gnomad4 OTH exome AF: 0.0132

GnomAD4 genome AF: 0.320 AC: 48637 AN: 152122 Hom.: 9994 Cov.: 33 AF XY: 0.315 AC XY: 23388 AN XY: 74350

Gnomad4 AFR AF: 0.0909

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.0484

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.465

Gnomad4 OTH AF: 0.329

Alfa AF: 0.407 Hom.: 8295

Bravo AF: 0.299

TwinsUK AF: 0.467 AC: 1730

ALSPAC AF: 0.459 AC: 1770

ExAC AF: 0.148 AC: 485

Asia WGS AF: 0.119 AC: 416 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.3
DANN	Benign	0.41
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.000019	T
MutationTaster	Benign	1.0	P;P;P
GERP RS		0.39

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: rs12982980; hg19: chr19-53349850;