19-12505484-G-C

Variant names:

• chr19-12505484-G-C
• rs10412981
• ENST00000428311.1:c.4-38634C>G

Variant summary

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

The ENST00000428311.1(ENSG00000196826):​c.4-38634C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 150,432 control chromosomes in the GnomAD database, including 41,708 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 0.74 (41708 hom., cov: 26)
• Consequence: ENSG00000196826 ENST00000428311.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 1 publications found

Genes affected

ENSG00000196826 (HGNC:):

ZNF709 (HGNC:20629): (zinc finger protein 709) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription 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]

MTCO2P27 (HGNC:52156): (MT-CO2 pseudogene 27)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000428311.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000196826	ENST00000428311.1	TSL:2	c.4-38634C>G		intron	N/A	ENSP00000404127.1
	ZNF709	ENST00000455490.1	TSL:2	c.90+8260C>G		intron	N/A	ENSP00000398085.1	H7C129
	MTCO2P27	ENST00000420740.1	TSL:6	n.116-180G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.743 AC: 111643 AN: 150314 Hom.: 41676 Cov.: 26

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.704

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.738

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

GnomAD4 genome AF: 0.743 AC: 111731 AN: 150432 Hom.: 41708 Cov.: 26 AF XY: 0.739 AC XY: 54269 AN XY: 73452

African (AFR) AF: 0.745 AC: 30558 AN: 40992

American (AMR) AF: 0.748 AC: 11318 AN: 15122

Ashkenazi Jewish (ASJ) AF: 0.708 AC: 2446 AN: 3454

East Asian (EAS) AF: 0.432 AC: 2189 AN: 5064

South Asian (SAS) AF: 0.673 AC: 3184 AN: 4728

European-Finnish (FIN) AF: 0.770 AC: 7977 AN: 10354

Middle Eastern (MID) AF: 0.701 AC: 199 AN: 284

European-Non Finnish (NFE) AF: 0.763 AC: 51486 AN: 67454

Other (OTH) AF: 0.740 AC: 1543 AN: 2084

Alfa AF: 0.666 Hom.: 1831

Bravo AF: 0.741

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.85
DANN	Benign	0.21
PhyloP100		-1.4

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10412981;

hg19: chr19-12616298;