Genetic Variant ZGRF1:c.-53T>A (chr4-112633229-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_018392.5(ZGRF1):c.-53T>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 1,409,646 control chromosomes in the GnomAD database, including 131,689 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 0.39 ( 12009 hom., cov: 32)

Exomes 𝑓: 0.44 ( 119680 hom. )

Consequence

ZGRF1
NM_018392.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.18

Publications

7 publications found

Variant links:

Genes affected

ZGRF1 (HGNC:25654): (zinc finger GRF-type containing 1) The encoded protein contains GRF zinc finger (zf-GRF) and transmembrane domains. GRF zinc fingers are found in a number of DNA-binding proteins. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2017]

ZGRF1 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=-0.75).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZGRF1	NM_018392.5 link	c.-53T>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 28	ENST00000505019.6	NP_060862.3	Q86YA3-1
ZGRF1	NM_018392.5 link	c.-53T>A		5_prime_UTR_variant	Exon 2 of 28	ENST00000505019.6	NP_060862.3	Q86YA3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZGRF1	ENST00000505019.6 link	c.-53T>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 28	5	NM_018392.5	ENSP00000424737.1		Q86YA3-1
ZGRF1	ENST00000505019.6 link	c.-53T>A		5_prime_UTR_variant	Exon 2 of 28	5	NM_018392.5	ENSP00000424737.1		Q86YA3-1

Frequencies

GnomAD3 genomes

AF:

0.393

AC:

59794

AN:

151980

Hom.:

12012

Cov.:

show subpopulations

Gnomad AFR

AF:

0.317

Gnomad AMI

AF:

0.270

Gnomad AMR

AF:

0.481

Gnomad ASJ

AF:

0.311

Gnomad EAS

AF:

0.395

Gnomad SAS

AF:

0.488

Gnomad FIN

AF:

0.398

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.419

Gnomad OTH

AF:

0.387

GnomAD4 exome

AF:

0.437

AC:

549933

AN:

1257548

Hom.:

119680

Cov.:

AF XY:

0.438

AC XY:

278184

AN XY:

635300

show subpopulations

African (AFR)

AF:

0.319

AC:

9119

AN:

28630

American (AMR)

AF:

0.564

AC:

22660

AN:

40168

Ashkenazi Jewish (ASJ)

AF:

0.308

AC:

7551

AN:

24518

East Asian (EAS)

AF:

0.421

AC:

16209

AN:

38542

South Asian (SAS)

AF:

0.497

AC:

39461

AN:

79370

European-Finnish (FIN)

AF:

0.419

AC:

22269

AN:

53186

Middle Eastern (MID)

AF:

0.380

AC:

1905

AN:

5010

European-Non Finnish (NFE)

AF:

0.437

AC:

408308

AN:

934754

Other (OTH)

AF:

0.421

AC:

22451

AN:

53370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

15155

30309

45464

60618

75773

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.393

AC:

59817

AN:

152098

Hom.:

12009

Cov.:

AF XY:

0.394

AC XY:

29301

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.316

AC:

13127

AN:

41496

American (AMR)

AF:

0.482

AC:

7350

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.311

AC:

1078

AN:

3470

East Asian (EAS)

AF:

0.395

AC:

2046

AN:

5178

South Asian (SAS)

AF:

0.489

AC:

2362

AN:

4828

European-Finnish (FIN)

AF:

0.398

AC:

4217

AN:

10590

Middle Eastern (MID)

AF:

0.332

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.419

AC:

28478

AN:

67966

Other (OTH)

AF:

0.387

AC:

816

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1862

3724

5587

7449

9311

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.397

Hom.:

1596

Bravo

AF:

0.395

Asia WGS

AF:

0.492

AC:

1705

AN:

3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

2.2

PromoterAI

-0.016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=295/5

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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4-112633229-A-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over