Variant 4-358406-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_003441.4(ZNF141):c.226+13976G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 286,954 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 13 hom., cov: 31)

Exomes 𝑓: 0.015 ( 31 hom. )

Consequence

ZNF141
NM_003441.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.194

Variant links:

Genes affected

ZNF141 (HGNC:12926): (zinc finger protein 141) The protein encoded by this gene is a zinc finger protein that may be a tumor suppressor. Defects in this gene have been associated with autosomal recessive postaxial polydactyly type A. [provided by RefSeq, Jan 2017]

ZNF141 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 4-358406-G-A is Benign according to our data. Variant chr4-358406-G-A is described in ClinVar as [Benign]. Clinvar id is 3043123.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0124 (1864/150836) while in subpopulation SAS AF= 0.0199 (95/4770). AF 95% confidence interval is 0.0167. There are 13 homozygotes in gnomad4. There are 892 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF141	NM_003441.4 linkuse as main transcript	c.226+13976G>A		intron_variant		ENST00000240499.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF141	ENST00000240499.8 linkuse as main transcript	c.226+13976G>A		intron_variant		1	NM_003441.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0124

AC:

1862

AN:

150720

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00888

Gnomad AMI

AF:

0.00221

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.00896

Gnomad EAS

AF:

0.000200

Gnomad SAS

AF:

0.0197

Gnomad FIN

AF:

0.00290

Gnomad MID

AF:

0.0458

Gnomad NFE

AF:

0.0166

Gnomad OTH

AF:

0.0183

GnomAD3 exomes

AF:

0.0137

AC:

184

AN:

13468

Hom.:

AF XY:

0.0137

AC XY:

100

AN XY:

7300

show subpopulations

Gnomad AFR exome

AF:

0.00654

Gnomad AMR exome

AF:

0.0133

Gnomad ASJ exome

AF:

0.00966

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0223

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0160

Gnomad OTH exome

AF:

0.0107

GnomAD4 exome

AF:

0.0148

AC:

2011

AN:

136118

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

1219

AN XY:

76924

show subpopulations

Gnomad4 AFR exome

AF:

0.00985

Gnomad4 AMR exome

AF:

0.0142

Gnomad4 ASJ exome

AF:

0.0112

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0226

Gnomad4 FIN exome

AF:

0.00347

Gnomad4 NFE exome

AF:

0.0136

Gnomad4 OTH exome

AF:

0.0123

GnomAD4 genome

AF:

0.0124

AC:

1864

AN:

150836

Hom.:

Cov.:

AF XY:

0.0121

AC XY:

892

AN XY:

73674

show subpopulations

Gnomad4 AFR

AF:

0.00893

Gnomad4 AMR

AF:

0.0107

Gnomad4 ASJ

AF:

0.00896

Gnomad4 EAS

AF:

0.000200

Gnomad4 SAS

AF:

0.0199

Gnomad4 FIN

AF:

0.00290

Gnomad4 NFE

AF:

0.0166

Gnomad4 OTH

AF:

0.0181

Alfa

AF:

0.0151

Hom.:

Bravo

AF:

0.0134

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ZNF141-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.6

DANN

Benign

0.59

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

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