rs7988

chr20-23372048-C-Achr20-23372048-C-Gchr20-23372048-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022482.5(GZF1):c.*1607C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,454 control chromosomes in the GnomAD database, including 6,458 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 0.29 (6446 hom., cov: 33)
  • Exomes 𝑓: 0.26 (12 hom.)
• Consequence: GZF1 NM_022482.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172

Genes affected

GZF1 (HGNC:15808): (GDNF inducible zinc finger protein 1) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GZF1	NM_022482.5	c.*1607C>A		3_prime_UTR_variant	6/6	ENST00000338121.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GZF1	ENST00000338121.10	c.*1607C>A		3_prime_UTR_variant	6/6	1	NM_022482.5	P1
GZF1	ENST00000377051.2	c.*1607C>A		3_prime_UTR_variant	5/5	1		P1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 43985 AN: 151902 Hom.: 6443 Cov.: 33

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.294

GnomAD4 exome AF: 0.265 AC: 115 AN: 434 Hom.: 12 Cov.: 0 AF XY: 0.256 AC XY: 67 AN XY: 262

Gnomad4 FIN exome AF: 0.265

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.289 AC: 44002 AN: 152020 Hom.: 6446 Cov.: 33 AF XY: 0.292 AC XY: 21693 AN XY: 74298

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.293

Alfa AF: 0.308 Hom.: 12427

Bravo AF: 0.293

Asia WGS AF: 0.293 AC: 1019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	7.2
Dann	Benign	0.62

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

Other links and lift over

dbSNP: rs7988; hg19: chr20-23352685; COSMIC: COSV57636443; COSMIC: COSV57636443;