rs10518257

chr19-22501274-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NR_160728.1(LOC105376917):n.147+31065A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00745 in 152,310 control chromosomes in the GnomAD database, including 12 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 0.0075 (12 hom., cov: 33)
• Consequence: LOC105376917 NR_160728.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.799

Genes affected

LOC105376917 (HGNC:):

ZNF98 (HGNC:13174): (zinc finger protein 98) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [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=-0.83).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00745 (1135/152310) while in subpopulation EAS AF= 0.0216 (112/5180). AF 95% confidence interval is 0.0184. There are 12 homozygotes in gnomad4. There are 560 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105376917	NR_160728.1	n.147+31065A>G		intron_variant, non_coding_transcript_variant
LOC105376917	NR_160727.1	n.414+13090A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF98	ENST00000593802.1	c.315+13090A>G		intron_variant		3
ZNF98	ENST00000599879.1	n.147+31065A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00744 AC: 1132 AN: 152192 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.00900

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00635

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.0218

Gnomad SAS AF: 0.00870

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00507

Gnomad OTH AF: 0.0129

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

GnomAD4 genome AF: 0.00745 AC: 1135 AN: 152310 Hom.: 12 Cov.: 33 AF XY: 0.00752 AC XY: 560 AN XY: 74480

Gnomad4 AFR AF: 0.00909

Gnomad4 AMR AF: 0.00635

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.0216

Gnomad4 SAS AF: 0.00829

Gnomad4 FIN AF: 0.00160

Gnomad4 NFE AF: 0.00507

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.00648 Hom.: 1

Bravo AF: 0.00832

Asia WGS AF: 0.0180 AC: 64 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	13
Dann	Benign	0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10518257; hg19: chr19-22684076;