Variant 7-64068891-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001159522.3(ZNF727):c.4C>T(p.Arg2Ter) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,589,956 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 51 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 47 hom. )

Consequence

ZNF727
NM_001159522.3 stop_gained, splice_region

Scores

Splicing: ADA: 0.00005457

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.36

Variant links:

Genes affected

ZNF727 (HGNC:22785): (zinc finger protein 727) 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF727 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 7-64068891-C-T is Benign according to our data. Variant chr7-64068891-C-T is described in ClinVar as [Benign]. Clinvar id is 787051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0136 (2072/152096) while in subpopulation AFR AF= 0.047 (1951/41498). AF 95% confidence interval is 0.0453. There are 51 homozygotes in gnomad4. There are 991 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 51 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF727	NM_001159522.3 linkuse as main transcript	c.4C>T	p.Arg2Ter	stop_gained, splice_region_variant	2/4	ENST00000456806.3	NP_001152994.1
ZNF727	XM_017012225.3 linkuse as main transcript	c.4C>T	p.Arg2Ter	stop_gained, splice_region_variant	2/3		XP_016867714.1
ZNF727	XR_242241.4 linkuse as main transcript	n.192C>T		splice_region_variant, non_coding_transcript_exon_variant	2/5
ZNF727	XR_927469.2 linkuse as main transcript	n.192C>T		splice_region_variant, non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF727	ENST00000456806.3 linkuse as main transcript	c.4C>T	p.Arg2Ter	stop_gained, splice_region_variant	2/4	4	NM_001159522.3	ENSP00000485448	P1

Frequencies

GnomAD3 genomes

AF:

0.0136

AC:

2065

AN:

151978

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0470

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00525

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000773

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00720

GnomAD3 exomes

AF:

0.00354

AC:

769

AN:

217012

Hom.:

AF XY:

0.00283

AC XY:

332

AN XY:

117344

show subpopulations

Gnomad AFR exome

AF:

0.0482

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000191

Gnomad SAS exome

AF:

0.000108

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000295

Gnomad OTH exome

AF:

0.00274

GnomAD4 exome

AF:

0.00162

AC:

2330

AN:

1437860

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

995

AN XY:

713536

show subpopulations

Gnomad4 AFR exome

AF:

0.0485

Gnomad4 AMR exome

AF:

0.00355

Gnomad4 ASJ exome

AF:

0.0000388

Gnomad4 EAS exome

AF:

0.00224

Gnomad4 SAS exome

AF:

0.0000597

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000261

Gnomad4 OTH exome

AF:

0.00350

GnomAD4 genome

AF:

0.0136

AC:

2072

AN:

152096

Hom.:

Cov.:

AF XY:

0.0133

AC XY:

991

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0470

Gnomad4 AMR

AF:

0.00524

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000775

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00712

Alfa

AF:

0.00309

Hom.:

Bravo

AF:

0.0159

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0376

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00390

AC:

470

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Benign

0.94

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.010

MutationTaster

Benign

1.0

Vest4

0.030

GERP RS

-0.30

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000055

dbscSNV1_RF

Benign

0.092

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over