rs2617729

Positions:

• chr19-53450618-T-A

Variant summary

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

The NM_001289951.2(ZNF761):​c.142+980T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,188 control chromosomes in the GnomAD database, including 1,700 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 0.15 (1700 hom., cov: 32)
• Consequence: ZNF761 NM_001289951.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200

Genes affected

ZNF761 (HGNC:23179): (zinc finger protein 761) 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]

ZNF765-ZNF761 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF761	NM_001289951.2	c.142+980T>A		intron_variant		ENST00000684525.1	NP_001276880.1
ZNF765-ZNF761	NM_001350496.2	c.142+980T>A		intron_variant			NP_001337425.1
ZNF761	NM_001008401.4	c.142+980T>A		intron_variant			NP_001008401.3
ZNF761	NM_001289952.1	c.142+980T>A		intron_variant			NP_001276881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF761	ENST00000684525.1	c.142+980T>A		intron_variant			NM_001289951.2	ENSP00000507666	P1
	ENST00000657048.1	n.87-14143A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22314 AN: 152070 Hom.: 1698 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.147 AC: 22327 AN: 152188 Hom.: 1700 Cov.: 32 AF XY: 0.147 AC XY: 10924 AN XY: 74412

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.152

Alfa AF: 0.153 Hom.: 226

Bravo AF: 0.153

Asia WGS AF: 0.115 AC: 403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.6
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2617729; hg19: chr19-53953872; COSMIC: COSV61888676; COSMIC: COSV61888676;