chr2-179483518-T-G

Variant names:

• chr2-179483518-T-G
• rs2271759
• NM_152520.6:c.553-84A>C

Variant summary

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

The NM_152520.6(ZNF385B):​c.553-84A>C variant causes a intron change. The variant allele was found at a frequency of 0.291 in 1,556,866 control chromosomes in the GnomAD database, including 67,223 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 0.31 (7558 hom., cov: 32)
  • Exomes 𝑓: 0.29 (59665 hom.)
• Consequence: ZNF385B NM_152520.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.70
• Publications: 7 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152520.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF385B	NM_152520.6	MANE Select	c.553-84A>C		intron	N/A	NP_689733.4
	ZNF385B	NM_001352809.2		c.691-84A>C		intron	N/A	NP_001339738.1
	ZNF385B	NM_001352810.2		c.553-84A>C		intron	N/A	NP_001339739.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF385B	ENST00000410066.7	TSL:1 MANE Select	c.553-84A>C		intron	N/A	ENSP00000386845.2
	ZNF385B	ENST00000466398.5	TSL:1	n.782-84A>C		intron	N/A
	ZNF385B	ENST00000409343.5	TSL:2	c.280-84A>C		intron	N/A	ENSP00000386379.1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47095 AN: 151896 Hom.: 7546 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.289 AC: 405866 AN: 1404852 Hom.: 59665 AF XY: 0.289 AC XY: 201422 AN XY: 697960

African (AFR) AF: 0.368 AC: 11886 AN: 32282

American (AMR) AF: 0.298 AC: 12711 AN: 42636

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 6418 AN: 24318

East Asian (EAS) AF: 0.429 AC: 16792 AN: 39126

South Asian (SAS) AF: 0.279 AC: 22601 AN: 81030

European-Finnish (FIN) AF: 0.290 AC: 14975 AN: 51670

Middle Eastern (MID) AF: 0.232 AC: 947 AN: 4088

European-Non Finnish (NFE) AF: 0.282 AC: 302267 AN: 1071538

Other (OTH) AF: 0.297 AC: 17269 AN: 58164

GnomAD4 genome AF: 0.310 AC: 47156 AN: 152014 Hom.: 7558 Cov.: 32 AF XY: 0.311 AC XY: 23070 AN XY: 74298

African (AFR) AF: 0.365 AC: 15136 AN: 41448

American (AMR) AF: 0.272 AC: 4152 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 945 AN: 3466

East Asian (EAS) AF: 0.439 AC: 2272 AN: 5178

South Asian (SAS) AF: 0.278 AC: 1339 AN: 4816

European-Finnish (FIN) AF: 0.297 AC: 3143 AN: 10576

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19251 AN: 67952

Other (OTH) AF: 0.297 AC: 626 AN: 2108

Alfa AF: 0.295 Hom.: 5651

Bravo AF: 0.313

Asia WGS AF: 0.421 AC: 1460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.78
PhyloP100		3.7
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: rs2271759; hg19: chr2-180348245; COSMIC: COSV61177889;