rs10487075

Positions:

• chr7-89335707-G-A
• chr7-89335707-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000333190.5(ZNF804B):​c.2725G>A​(p.Glu909Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0959 in 1,613,950 control chromosomes in the GnomAD database, including 8,100 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.074 (551 hom., cov: 32)
  • Exomes 𝑓: 0.098 (7549 hom.)
• Consequence: ZNF804B ENST00000333190.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.387

Genes affected

ZNF804B (HGNC:21958): (zinc finger protein 804B) Predicted to enable metal ion binding activity. Predicted to be active 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 (MetaRNN=0.0020000637).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF804B	NM_181646.5	c.2725G>A	p.Glu909Lys	missense_variant	4/4	ENST00000333190.5	NP_857597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF804B	ENST00000333190.5	c.2725G>A	p.Glu909Lys	missense_variant	4/4	1	NM_181646.5	ENSP00000329638	P1
ZNF804B	ENST00000611114.1	c.2476G>A	p.Glu826Lys	missense_variant	3/3	5		ENSP00000478506

Frequencies

GnomAD3 genomes AF: 0.0745 AC: 11326 AN: 152066 Hom.: 550 Cov.: 32

Gnomad AFR AF: 0.0179

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0544

Gnomad ASJ AF: 0.0844

Gnomad EAS AF: 0.0632

Gnomad SAS AF: 0.0588

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0755

GnomAD3 exomes AF: 0.0819 AC: 20570 AN: 251288 Hom.: 987 AF XY: 0.0836 AC XY: 11350 AN XY: 135804

Gnomad AFR exome AF: 0.0171

Gnomad AMR exome AF: 0.0401

Gnomad ASJ exome AF: 0.0855

Gnomad EAS exome AF: 0.0589

Gnomad SAS exome AF: 0.0555

Gnomad FIN exome AF: 0.128

Gnomad NFE exome AF: 0.105

Gnomad OTH exome AF: 0.0930

GnomAD4 exome AF: 0.0982 AC: 143476 AN: 1461766 Hom.: 7549 Cov.: 38 AF XY: 0.0969 AC XY: 70486 AN XY: 727186

Gnomad4 AFR exome AF: 0.0142

Gnomad4 AMR exome AF: 0.0415

Gnomad4 ASJ exome AF: 0.0830

Gnomad4 EAS exome AF: 0.0724

Gnomad4 SAS exome AF: 0.0586

Gnomad4 FIN exome AF: 0.131

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.0911

GnomAD4 genome AF: 0.0744 AC: 11330 AN: 152184 Hom.: 551 Cov.: 32 AF XY: 0.0742 AC XY: 5522 AN XY: 74388

Gnomad4 AFR AF: 0.0178

Gnomad4 AMR AF: 0.0543

Gnomad4 ASJ AF: 0.0844

Gnomad4 EAS AF: 0.0633

Gnomad4 SAS AF: 0.0591

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.0775

Alfa AF: 0.0974 Hom.: 1483

Bravo AF: 0.0660

TwinsUK AF: 0.103 AC: 381

ALSPAC AF: 0.114 AC: 439

ESP6500AA AF: 0.0238 AC: 105

ESP6500EA AF: 0.107 AC: 917

ExAC AF: 0.0812 AC: 9863

Asia WGS AF: 0.0590 AC: 205 AN: 3478

EpiCase AF: 0.101

EpiControl AF: 0.104

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0042	T;.
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.62	T;T
MetaRNN	Benign	0.0020	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	2.0	M;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.87	N;.
REVEL	Benign	0.10
Sift	Uncertain	0.011	D;.
Sift4G	Benign	0.087	T;D
Polyphen		0.0020	B;.
Vest4		0.027
MPC		0.048
ClinPred		0.0033	T
GERP RS		2.0
Varity_R		0.10
gMVP		0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs10487075; hg19: chr7-88965021;