rs2304130

Positions:

• chr19-19678719-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_033204.4(ZNF101):​c.131-7A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0925 in 1,598,448 control chromosomes in the GnomAD database, including 7,870 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1278 hom., cov: 32)
  • Exomes 𝑓: 0.090 (6592 hom.)
• Consequence: ZNF101 NM_033204.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001036
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240

Genes affected

ZNF101 (HGNC:12881): (zinc finger protein 101) Zinc finger proteins (ZNFs), such as ZNF101, bind nucleic acids and perform many key functions, the most important of which is regulating transcription (summary by Bellefroid et al., 1993 [PubMed 8467795]). See ZNF91 (MIM 603971) for general information on ZNFs.[supplied by OMIM, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF101	NM_033204.4	c.131-7A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000592502.2	NP_149981.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF101	ENST00000592502.2	c.131-7A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_033204.4	ENSP00000468049	P1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17693 AN: 151970 Hom.: 1274 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0530

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.0782

Gnomad OTH AF: 0.103

GnomAD3 exomes AF: 0.103 AC: 24836 AN: 242298 Hom.: 1540 AF XY: 0.101 AC XY: 13201 AN XY: 131152

Gnomad AFR exome AF: 0.191

Gnomad AMR exome AF: 0.128

Gnomad ASJ exome AF: 0.0381

Gnomad EAS exome AF: 0.131

Gnomad SAS exome AF: 0.143

Gnomad FIN exome AF: 0.0545

Gnomad NFE exome AF: 0.0833

Gnomad OTH exome AF: 0.0861

GnomAD4 exome AF: 0.0899 AC: 130094 AN: 1446360 Hom.: 6592 Cov.: 29 AF XY: 0.0906 AC XY: 65225 AN XY: 719684

Gnomad4 AFR exome AF: 0.193

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.0385

Gnomad4 EAS exome AF: 0.122

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.0584

Gnomad4 NFE exome AF: 0.0830

Gnomad4 OTH exome AF: 0.0940

GnomAD4 genome AF: 0.116 AC: 17712 AN: 152088 Hom.: 1278 Cov.: 32 AF XY: 0.116 AC XY: 8654 AN XY: 74372

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.0357

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.0530

Gnomad4 NFE AF: 0.0782

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0859 Hom.: 1690

Bravo AF: 0.126

Asia WGS AF: 0.155 AC: 540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	5.7
DANN	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00010
dbscSNV1_RF	Benign	0.0060
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: rs2304130; hg19: chr19-19789528; COSMIC: COSV58909629; COSMIC: COSV58909629;