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GeneBe

6-27451555-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001318891.2(ZNF184):c.2004G>A(p.Lys668=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,614,034 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 36 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 32 hom. )

Consequence

ZNF184
NM_001318891.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0230
Variant links:
Genes affected
ZNF184 (HGNC:12975): (zinc finger protein 184) The protein encoded by this gene is predicted to be a Kruppel C2H2-type zinc-finger protein family member. Sequence analysis predicts that the protein contains two Kruppel associated box (KRAB) boxes in the N-terminus and highly conserved zinc finger motifs at the C-terminus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-27451555-C-T is Benign according to our data. Variant chr6-27451555-C-T is described in ClinVar as [Benign]. Clinvar id is 790032.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.023 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0113 (1715/152206) while in subpopulation AFR AF= 0.0395 (1639/41516). AF 95% confidence interval is 0.0379. There are 36 homozygotes in gnomad4. There are 805 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 36 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF184NM_001318891.2 linkuse as main transcriptc.2004G>A p.Lys668= synonymous_variant 6/6 ENST00000683788.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF184ENST00000683788.1 linkuse as main transcriptc.2004G>A p.Lys668= synonymous_variant 6/6 NM_001318891.2 P1
ZNF184ENST00000211936.10 linkuse as main transcriptc.2004G>A p.Lys668= synonymous_variant 6/61 P1
ZNF184ENST00000377419.1 linkuse as main transcriptc.2004G>A p.Lys668= synonymous_variant 6/64 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0113
AC:
1712
AN:
152088
Hom.:
36
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0395
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00341
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00718
GnomAD3 exomes
AF:
0.00283
AC:
711
AN:
251156
Hom.:
13
AF XY:
0.00202
AC XY:
274
AN XY:
135738
show subpopulations
Gnomad AFR exome
AF:
0.0384
Gnomad AMR exome
AF:
0.00194
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000705
Gnomad OTH exome
AF:
0.00114
GnomAD4 exome
AF:
0.00119
AC:
1740
AN:
1461828
Hom.:
32
Cov.:
31
AF XY:
0.00101
AC XY:
738
AN XY:
727210
show subpopulations
Gnomad4 AFR exome
AF:
0.0425
Gnomad4 AMR exome
AF:
0.00235
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000612
Gnomad4 OTH exome
AF:
0.00205
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0113
AC:
1715
AN:
152206
Hom.:
36
Cov.:
32
AF XY:
0.0108
AC XY:
805
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.0395
Gnomad4 AMR
AF:
0.00340
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00710
Alfa
AF:
0.00501
Hom.:
3
Bravo
AF:
0.0131
Asia WGS
AF:
0.00260
AC:
9
AN:
3478
EpiCase
AF:
0.000273
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
Cadd
Benign
6.1
Dann
Benign
0.77

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.

Other links and lift over

dbSNP: rs73741730; hg19: chr6-27419334; API