2-179779127-T-C

Variant names:

• chr2-179779127-T-C
• rs4894122
• NM_152520.6:c.-154-8455A>G

Variant summary

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

The NM_152520.6(ZNF385B):​c.-154-8455A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,234 control chromosomes in the GnomAD database, including 1,056 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 0.10 (1056 hom., cov: 32)
• Consequence: ZNF385B NM_152520.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.688
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF385B	NM_152520.6	c.-154-8455A>G		intron_variant	Intron 1 of 9	ENST00000410066.7	NP_689733.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF385B	ENST00000410066.7	c.-154-8455A>G		intron_variant	Intron 1 of 9	1	NM_152520.6	ENSP00000386845.2
ZNF385B	ENST00000451732.6	c.-154-8455A>G		intron_variant	Intron 1 of 2	4		ENSP00000409978.2
ZNF385B	ENST00000438871.2	c.-154-8455A>G		intron_variant	Intron 1 of 2	3		ENSP00000400232.2

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15514 AN: 152116 Hom.: 1051 Cov.: 32

Gnomad AFR AF: 0.0273

Gnomad AMI AF: 0.0806

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0316

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0827

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.102 AC: 15517 AN: 152234 Hom.: 1056 Cov.: 32 AF XY: 0.101 AC XY: 7546 AN XY: 74444

African (AFR) AF: 0.0272 AC: 1129 AN: 41556

American (AMR) AF: 0.178 AC: 2718 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 489 AN: 3468

East Asian (EAS) AF: 0.0314 AC: 163 AN: 5184

South Asian (SAS) AF: 0.146 AC: 705 AN: 4824

European-Finnish (FIN) AF: 0.0827 AC: 877 AN: 10606

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9091 AN: 68000

Other (OTH) AF: 0.113 AC: 239 AN: 2112

Alfa AF: 0.116 Hom.: 655

Bravo AF: 0.106

Asia WGS AF: 0.0980 AC: 340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.15
DANN	Benign	0.62
PhyloP100		-0.69
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: rs4894122; hg19: chr2-180643854;