rs2304130

Variant names:

• chr19-19678719-A-G
• rs2304130
• NM_033204.4:c.131-7A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_033204.4(ZNF101):​c.131-7A>G variant causes a splice region, 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, 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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZNF101	NM_033204.4	c.131-7A>G		splice_region_variant, intron_variant	Intron 2 of 3	ENST00000592502.2	NP_149981.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF101	ENST00000592502.2	c.131-7A>G		splice_region_variant, intron_variant	Intron 2 of 3	1	NM_033204.4	ENSP00000468049.1

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

GnomAD2 exomes AF: 0.103 AC: 24836 AN: 242298 AF XY: 0.101

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 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 AC: 6308 AN: 32680

Gnomad4 AMR exome AF: 0.131 AC: 5526 AN: 42038

Gnomad4 ASJ exome AF: 0.0385 AC: 993 AN: 25764

Gnomad4 EAS exome AF: 0.122 AC: 4811 AN: 39540

Gnomad4 SAS exome AF: 0.141 AC: 11761 AN: 83370

Gnomad4 FIN exome AF: 0.0584 AC: 3114 AN: 53280

Gnomad4 NFE exome AF: 0.0830 AC: 91722 AN: 1105244

Gnomad4 Remaining exome AF: 0.0940 AC: 5614 AN: 59700

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 AC: 0.191207 AN: 0.191207

Gnomad4 AMR AF: 0.134 AC: 0.134041 AN: 0.134041

Gnomad4 ASJ AF: 0.0357 AC: 0.0357349 AN: 0.0357349

Gnomad4 EAS AF: 0.130 AC: 0.130208 AN: 0.130208

Gnomad4 SAS AF: 0.151 AC: 0.151057 AN: 0.151057

Gnomad4 FIN AF: 0.0530 AC: 0.0529645 AN: 0.0529645

Gnomad4 NFE AF: 0.0782 AC: 0.0782151 AN: 0.0782151

Gnomad4 OTH AF: 0.102 AC: 0.102176 AN: 0.102176

Alfa AF: 0.0901 Hom.: 3528

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
Mutation Taster		=100/0	polymorphism (auto)

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;