4-112624951-G-T

Variant names:

• chr4-112624951-G-T
• rs1471880
• NM_018392.5:c.103-1075C>A

Variant summary

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

The NM_018392.5(ZGRF1):​c.103-1075C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,852 control chromosomes in the GnomAD database, including 15,200 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 0.45 (15200 hom., cov: 31)
• Consequence: ZGRF1 NM_018392.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZGRF1	NM_018392.5	c.103-1075C>A		intron_variant	Intron 3 of 27	ENST00000505019.6	NP_060862.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZGRF1	ENST00000505019.6	c.103-1075C>A		intron_variant	Intron 3 of 27	5	NM_018392.5	ENSP00000424737.1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67534 AN: 151734 Hom.: 15186 Cov.: 31

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.422

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.445 AC: 67589 AN: 151852 Hom.: 15200 Cov.: 31 AF XY: 0.444 AC XY: 32997 AN XY: 74262

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.522

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.421

Alfa AF: 0.432 Hom.: 13544

Bravo AF: 0.455

Asia WGS AF: 0.528 AC: 1836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.64

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: rs1471880; hg19: chr4-113546107;