Genetic Variant ZNF667:c.-548-819A>G (chr19-56473006-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001321356.2(ZNF667):c.-548-819A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 152,144 control chromosomes in the GnomAD database, including 11,692 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 0.38 ( 11692 hom., cov: 32)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

ZNF667
NM_001321356.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.844

Publications

7 publications found

Variant links:

Genes affected

ZNF667 (HGNC:28854): (zinc finger protein 667) Predicted to enable DNA-binding transcription factor activity 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 located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF667 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321356.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZNF667	NM_001321356.2	MANE Select	c.-548-819A>G	intron	N/A	NP_001308285.1	Q5HYK9
ZNF667	NM_022103.4		c.-60+4266A>G	intron	N/A	NP_071386.3
ZNF667	NM_001321355.2		c.-332+4266A>G	intron	N/A	NP_001308284.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZNF667	ENST00000504904.8	TSL:2 MANE Select	c.-548-819A>G	intron	N/A	ENSP00000439402.1	Q5HYK9
ZNF667	ENST00000292069.10	TSL:1	c.-60+4266A>G	intron	N/A	ENSP00000292069.5	Q5HYK9
ZNF667	ENST00000591790.5	TSL:2	c.-1367A>G	5_prime_UTR	Exon 1 of 6	ENSP00000468550.2	M0QX02

Frequencies

GnomAD3 genomes

AF:

0.382

AC:

58058

AN:

152024

Hom.:

11690

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.362

Gnomad ASJ

AF:

0.527

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.382

Gnomad FIN

AF:

0.387

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.456

Gnomad OTH

AF:

0.406

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.382

AC:

58071

AN:

152142

Hom.:

11692

Cov.:

AF XY:

0.377

AC XY:

28058

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.291

AC:

12071

AN:

41512

American (AMR)

AF:

0.362

AC:

5527

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.527

AC:

1827

AN:

3468

East Asian (EAS)

AF:

0.100

AC:

518

AN:

5178

South Asian (SAS)

AF:

0.382

AC:

1841

AN:

4820

European-Finnish (FIN)

AF:

0.387

AC:

4094

AN:

10580

Middle Eastern (MID)

AF:

0.524

AC:

153

AN:

292

European-Non Finnish (NFE)

AF:

0.456

AC:

30973

AN:

67986

Other (OTH)

AF:

0.403

AC:

850

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1846

3692

5539

7385

9231

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

570

1140

1710

2280

2850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.429

Hom.:

37181

Bravo

AF:

0.374

Asia WGS

AF:

0.239

AC:

835

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.5

(source)

DANN

Benign

0.74

PhyloP100

-0.84

PromoterAI

0.00090

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over