19-37065416-T-C

Variant names:

• chr19-37065416-T-C
• rs1818748
• XR_001754095.2:n.10990A>G

Variant summary

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

The XR_001754095.2(LOC105372390):​n.10990A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 152,068 control chromosomes in the GnomAD database, including 21,037 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 0.52 (21037 hom., cov: 33)
• Consequence: LOC105372390 XR_001754095.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.415
• Publications: 2 publications found

Genes affected

LOC105372390 (HGNC:):

ZNF420 (HGNC:20649): (zinc finger protein 420) The protein encoded by this gene is a KRAB-type zinc finger protein that negatively-regulates p53-mediated apoptosis. Under stress conditions, the encoded protein is phosphorylated by ATM and dissociates from p53, which activates p53 and initiates apoptosis. [provided by RefSeq, Jul 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105372390	XR_001754095.2	n.10990A>G		non_coding_transcript_exon_variant	Exon 2 of 2
ZNF420	XM_011526503.3	c.-124-14929T>C		intron_variant	Intron 1 of 4		XP_011524805.1
ZNF420	XM_047438230.1	c.-157-14929T>C		intron_variant	Intron 1 of 5		XP_047294186.1
ZNF420	XM_011526510.3	c.-121-14929T>C		intron_variant	Intron 1 of 2		XP_011524812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF420	ENST00000587029.5	c.-124-14929T>C		intron_variant	Intron 1 of 4	4		ENSP00000466057.1
ZNF420	ENST00000590332.1	c.-78+57334T>C		intron_variant	Intron 1 of 1	4		ENSP00000468387.1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78294 AN: 151950 Hom.: 21000 Cov.: 33

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.516 AC: 78403 AN: 152068 Hom.: 21037 Cov.: 33 AF XY: 0.510 AC XY: 37895 AN XY: 74324

African (AFR) AF: 0.621 AC: 25777 AN: 41494

American (AMR) AF: 0.476 AC: 7273 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 1571 AN: 3470

East Asian (EAS) AF: 0.149 AC: 771 AN: 5168

South Asian (SAS) AF: 0.401 AC: 1934 AN: 4828

European-Finnish (FIN) AF: 0.500 AC: 5275 AN: 10544

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34312 AN: 67960

Other (OTH) AF: 0.518 AC: 1094 AN: 2114

Alfa AF: 0.506 Hom.: 3104

Bravo AF: 0.519

Asia WGS AF: 0.336 AC: 1169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.4
DANN	Benign	0.92
PhyloP100		0.41

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1818748; hg19: chr19-37556318;