rs1916830

Positions:

• chr7-89333725-G-A

Variant summary

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

The NM_181646.5(ZNF804B):​c.743G>A​(p.Cys248Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0347 in 1,613,456 control chromosomes in the GnomAD database, including 7,354 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.041 (754 hom., cov: 32)
  • Exomes 𝑓: 0.034 (6600 hom.)
• Consequence: ZNF804B NM_181646.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.79

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=4.710853E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF804B	NM_181646.5	c.743G>A	p.Cys248Tyr	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.743G>A	p.Cys248Tyr	missense_variant	4/4	1	NM_181646.5	ENSP00000329638.4
ZNF804B	ENST00000611114.1	c.494G>A	p.Cys165Tyr	missense_variant	3/3	5		ENSP00000478506.1

Frequencies

GnomAD3 genomes AF: 0.0415 AC: 6305 AN: 151964 Hom.: 753 Cov.: 32

Gnomad AFR AF: 0.0191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.0132

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00603

Gnomad OTH AF: 0.0431

GnomAD3 exomes AF: 0.0882 AC: 22034 AN: 249928 Hom.: 3305 AF XY: 0.0817 AC XY: 11048 AN XY: 135218

Gnomad AFR exome AF: 0.0200

Gnomad AMR exome AF: 0.228

Gnomad ASJ exome AF: 0.0128

Gnomad EAS exome AF: 0.457

Gnomad SAS exome AF: 0.135

Gnomad FIN exome AF: 0.0117

Gnomad NFE exome AF: 0.00560

Gnomad OTH exome AF: 0.0567

GnomAD4 exome AF: 0.0340 AC: 49700 AN: 1461374 Hom.: 6600 Cov.: 32 AF XY: 0.0358 AC XY: 26036 AN XY: 726980

Gnomad4 AFR exome AF: 0.0189

Gnomad4 AMR exome AF: 0.212

Gnomad4 ASJ exome AF: 0.0120

Gnomad4 EAS exome AF: 0.455

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.0112

Gnomad4 NFE exome AF: 0.00549

Gnomad4 OTH exome AF: 0.0491

GnomAD4 genome AF: 0.0415 AC: 6309 AN: 152082 Hom.: 754 Cov.: 32 AF XY: 0.0466 AC XY: 3465 AN XY: 74328

Gnomad4 AFR AF: 0.0191

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.0110

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.0132

Gnomad4 NFE AF: 0.00603

Gnomad4 OTH AF: 0.0451

Alfa AF: 0.0262 Hom.: 1181

Bravo AF: 0.0510

TwinsUK AF: 0.00378 AC: 14

ALSPAC AF: 0.00441 AC: 17

ESP6500AA AF: 0.0184 AC: 81

ESP6500EA AF: 0.00628 AC: 54

ExAC AF: 0.0817 AC: 9918

Asia WGS AF: 0.300 AC: 1040 AN: 3478

EpiCase AF: 0.00551

EpiControl AF: 0.00481

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	17
DANN	Benign	0.32
DEOGEN2	Benign	0.018	T;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.74	T;T
MetaRNN	Benign	0.00047	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.0	D;.
REVEL	Benign	0.057
Sift	Benign	0.16	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.22	B;.
Vest4		0.055
MPC		0.058
ClinPred		0.030	T
GERP RS		4.2
Varity_R		0.12
gMVP		0.11

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: rs1916830; hg19: chr7-88963039; COSMIC: COSV60819436;