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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018392.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZGRF1	NM_018392.5	MANE Select	c.-53T>A	5_prime_UTR_premature_start_codon_gain	Exon 2 of 28	NP_060862.3
ZGRF1	NM_018392.5	MANE Select	c.-53T>A	5_prime_UTR	Exon 2 of 28	NP_060862.3
ZGRF1	NM_001350397.2		c.-53T>A	5_prime_UTR_premature_start_codon_gain	Exon 2 of 27	NP_001337326.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZGRF1	ENST00000505019.6	TSL:5 MANE Select	c.-53T>A	5_prime_UTR_premature_start_codon_gain	Exon 2 of 28	ENSP00000424737.1
ZGRF1	ENST00000309071.9	TSL:1	c.-53T>A	5_prime_UTR_premature_start_codon_gain	Exon 2 of 11	ENSP00000309095.5
ZGRF1	ENST00000505019.6	TSL:5 MANE Select	c.-53T>A	5_prime_UTR	Exon 2 of 28	ENSP00000424737.1

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

Age Distribution

Exome Het

Exome Hom

Variant carriers

11848

23696

35544

47392

59240

<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:

0.393

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

Age Distribution

Genome Het

Genome Hom

Variant carriers

580

1160

1740

2320

2900

<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:

0.397

Hom.:

1596

Bravo

AF:

0.395

Asia WGS

AF:

0.492

AC:

1705

AN:

3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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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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