NM_152520.6:c.716-2498A>G

Variant names:

• chr2-179449268-T-C
• rs6757845
• NM_152520.6:c.716-2498A>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.716-2498A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 151,850 control chromosomes in the GnomAD database, including 33,878 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 0.66 (33878 hom., cov: 31)
• Consequence: ZNF385B NM_152520.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.541
• Publications: 4 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=-0.53).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.91 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.716-2498A>G		intron	N/A	NP_689733.4
	ZNF385B	NM_001352809.2		c.854-2498A>G		intron	N/A	NP_001339738.1
	ZNF385B	NM_001352810.2		c.797-2498A>G		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.716-2498A>G		intron	N/A	ENSP00000386845.2
	ZNF385B	ENST00000466398.5	TSL:1	n.945-2498A>G		intron	N/A
	ZNF385B	ENST00000409343.5	TSL:2	c.443-2498A>G		intron	N/A	ENSP00000386379.1

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100147 AN: 151732 Hom.: 33824 Cov.: 31

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.932

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.660 AC: 100262 AN: 151850 Hom.: 33878 Cov.: 31 AF XY: 0.665 AC XY: 49339 AN XY: 74214

African (AFR) AF: 0.759 AC: 31467 AN: 41454

American (AMR) AF: 0.638 AC: 9709 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2106 AN: 3462

East Asian (EAS) AF: 0.932 AC: 4802 AN: 5150

South Asian (SAS) AF: 0.816 AC: 3935 AN: 4820

European-Finnish (FIN) AF: 0.637 AC: 6717 AN: 10540

Middle Eastern (MID) AF: 0.658 AC: 192 AN: 292

European-Non Finnish (NFE) AF: 0.582 AC: 39522 AN: 67892

Other (OTH) AF: 0.653 AC: 1376 AN: 2106

Alfa AF: 0.608 Hom.: 87267

Bravo AF: 0.661

Asia WGS AF: 0.855 AC: 2973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.7
DANN	Benign	0.47
PhyloP100		0.54
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: rs6757845; hg19: chr2-180313995;