rs16866933

Variant names:

• chr2-179701951-G-A
• rs16866933
• NM_152520.6:c.298+67552C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152520.6(ZNF385B):​c.298+67552C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0983 in 152,194 control chromosomes in the GnomAD database, including 1,165 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 0.098 (1165 hom., cov: 33)
• Consequence: ZNF385B NM_152520.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• Publications: 16 publications found

Genes affected

ZNF385B (HGNC:26332): (zinc finger protein 385B) Enables p53 binding activity. Involved in intrinsic apoptotic signaling pathway by p53 class mediator. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF385B	NM_152520.6	c.298+67552C>T		intron_variant	Intron 3 of 9	ENST00000410066.7	NP_689733.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF385B	ENST00000410066.7	c.298+67552C>T		intron_variant	Intron 3 of 9	1	NM_152520.6	ENSP00000386845.2
ZNF385B	ENST00000409343.5	c.25+43762C>T		intron_variant	Intron 1 of 7	2		ENSP00000386379.1
ZNF385B	ENST00000475539.5	n.142+43762C>T		intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes AF: 0.0981 AC: 14926 AN: 152076 Hom.: 1152 Cov.: 33

Gnomad AFR AF: 0.0589

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0772

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0834

Gnomad OTH AF: 0.0880

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

GnomAD4 genome AF: 0.0983 AC: 14962 AN: 152194 Hom.: 1165 Cov.: 33 AF XY: 0.106 AC XY: 7858 AN XY: 74398

African (AFR) AF: 0.0592 AC: 2459 AN: 41550

American (AMR) AF: 0.0770 AC: 1178 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 356 AN: 3468

East Asian (EAS) AF: 0.412 AC: 2129 AN: 5164

South Asian (SAS) AF: 0.214 AC: 1031 AN: 4820

European-Finnish (FIN) AF: 0.174 AC: 1844 AN: 10574

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0834 AC: 5673 AN: 68004

Other (OTH) AF: 0.0975 AC: 206 AN: 2112

Alfa AF: 0.0931 Hom.: 4019

Bravo AF: 0.0882

Asia WGS AF: 0.293 AC: 1018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.9
DANN	Benign	0.79
PhyloP100		-0.024
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16866933; hg19: chr2-180566678;