rs6510085

Variant names:

• chr19-57491451-T-A
• rs6510085
• NM_024691.4:c.73-20T>A

Your query was ambiguous. Multiple possible variants found:

• chr19-57491451-T-A
• chr19-57491451-T-C
• chr19-57491451-T-G

Variant summary

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

The NM_024691.4(ZNF419):​c.73-20T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 1,610,894 control chromosomes in the GnomAD database, including 395,717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.67 (34517 hom., cov: 30)
  • Exomes 𝑓: 0.70 (361200 hom.)
• Consequence: ZNF419 NM_024691.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125
• Publications: 14 publications found

Genes affected

ZNF419 (HGNC:20648): (zinc finger protein 419) 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]

ENSG00000268107 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024691.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF419	NM_024691.4	MANE Select	c.73-20T>A		intron	N/A	NP_078967.3
	ZNF419	NM_001098491.2		c.73-17T>A		intron	N/A	NP_001091961.1	Q96HQ0-5
	ZNF419	NM_001098492.2		c.34-17T>A		intron	N/A	NP_001091962.1	Q96HQ0-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF419	ENST00000221735.12	TSL:1 MANE Select	c.73-20T>A		intron	N/A	ENSP00000221735.7	Q96HQ0-1
	ZNF419	ENST00000424930.6	TSL:1	c.73-17T>A		intron	N/A	ENSP00000388864.1	Q96HQ0-5
	ZNF419	ENST00000523439.1	TSL:1	n.265-20T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102129 AN: 151734 Hom.: 34489 Cov.: 30

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.646

GnomAD2 exomes AF: 0.711 AC: 178385 AN: 250882 AF XY: 0.715

Gnomad AFR exome AF: 0.601

Gnomad AMR exome AF: 0.735

Gnomad ASJ exome AF: 0.662

Gnomad EAS exome AF: 0.718

Gnomad FIN exome AF: 0.728

Gnomad NFE exome AF: 0.699

Gnomad OTH exome AF: 0.703

GnomAD4 exome AF: 0.703 AC: 1025142 AN: 1459040 Hom.: 361200 Cov.: 58 AF XY: 0.704 AC XY: 510712 AN XY: 725304

African (AFR) AF: 0.601 AC: 20077 AN: 33430

American (AMR) AF: 0.726 AC: 32405 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 17059 AN: 26018

East Asian (EAS) AF: 0.737 AC: 29192 AN: 39612

South Asian (SAS) AF: 0.789 AC: 67991 AN: 86212

European-Finnish (FIN) AF: 0.730 AC: 38939 AN: 53370

Middle Eastern (MID) AF: 0.660 AC: 3800 AN: 5756

European-Non Finnish (NFE) AF: 0.697 AC: 773793 AN: 1109756

Other (OTH) AF: 0.695 AC: 41886 AN: 60250

GnomAD4 genome AF: 0.673 AC: 102210 AN: 151854 Hom.: 34517 Cov.: 30 AF XY: 0.675 AC XY: 50090 AN XY: 74210

African (AFR) AF: 0.608 AC: 25153 AN: 41396

American (AMR) AF: 0.664 AC: 10140 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2264 AN: 3470

East Asian (EAS) AF: 0.726 AC: 3714 AN: 5116

South Asian (SAS) AF: 0.805 AC: 3874 AN: 4814

European-Finnish (FIN) AF: 0.729 AC: 7701 AN: 10564

Middle Eastern (MID) AF: 0.664 AC: 194 AN: 292

European-Non Finnish (NFE) AF: 0.694 AC: 47127 AN: 67924

Other (OTH) AF: 0.645 AC: 1358 AN: 2104

Alfa AF: 0.680 Hom.: 6514

Bravo AF: 0.667

Asia WGS AF: 0.761 AC: 2645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.7
DANN	Benign	0.72
PhyloP100		-0.13
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: rs6510085; hg19: chr19-58002819;