rs749671

Variant names:

• chr16-31077026-G-A
• rs749671
• NM_014699.4:c.702G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-31077026-G-A
• chr16-31077026-G-C
• chr16-31077026-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014699.4(ZNF646):​c.702G>A​(p.Glu234Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,613,790 control chromosomes in the GnomAD database, including 123,514 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 0.32 (9819 hom., cov: 32)
  • Exomes 𝑓: 0.38 (113695 hom.)
• Consequence: ZNF646 NM_014699.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48
• Publications: 71 publications found

Genes affected

ZNF646 (HGNC:29004): (zinc finger protein 646) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=1.48 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF646	NM_014699.4	c.702G>A	p.Glu234Glu	synonymous_variant	Exon 2 of 3	ENST00000300850.5	NP_055514.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF646	ENST00000300850.5	c.702G>A	p.Glu234Glu	synonymous_variant	Exon 2 of 3	1	NM_014699.4	ENSP00000300850.5
ZNF646	ENST00000394979.2	c.702G>A	p.Glu234Glu	synonymous_variant	Exon 1 of 1	6		ENSP00000378429.2
ZNF646	ENST00000428260.1	c.702G>A	p.Glu234Glu	synonymous_variant	Exon 2 of 2	3		ENSP00000391271.1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 48028 AN: 152020 Hom.: 9818 Cov.: 32

Gnomad AFR AF: 0.0991

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.382

GnomAD2 exomes AF: 0.394 AC: 98881 AN: 250982 AF XY: 0.384

Gnomad AFR exome AF: 0.0947

Gnomad AMR exome AF: 0.454

Gnomad ASJ exome AF: 0.467

Gnomad EAS exome AF: 0.894

Gnomad FIN exome AF: 0.384

Gnomad NFE exome AF: 0.391

Gnomad OTH exome AF: 0.400

GnomAD4 exome AF: 0.377 AC: 551534 AN: 1461652 Hom.: 113695 Cov.: 70 AF XY: 0.373 AC XY: 271058 AN XY: 727096

African (AFR) AF: 0.0923 AC: 3091 AN: 33474

American (AMR) AF: 0.452 AC: 20201 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 12231 AN: 26134

East Asian (EAS) AF: 0.904 AC: 35869 AN: 39698

South Asian (SAS) AF: 0.183 AC: 15824 AN: 86256

European-Finnish (FIN) AF: 0.390 AC: 20812 AN: 53338

Middle Eastern (MID) AF: 0.455 AC: 2627 AN: 5768

European-Non Finnish (NFE) AF: 0.376 AC: 417572 AN: 1111896

Other (OTH) AF: 0.386 AC: 23307 AN: 60378

GnomAD4 genome AF: 0.316 AC: 48026 AN: 152138 Hom.: 9819 Cov.: 32 AF XY: 0.318 AC XY: 23679 AN XY: 74348

African (AFR) AF: 0.0988 AC: 4105 AN: 41536

American (AMR) AF: 0.389 AC: 5941 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1626 AN: 3470

East Asian (EAS) AF: 0.891 AC: 4601 AN: 5162

South Asian (SAS) AF: 0.177 AC: 855 AN: 4822

European-Finnish (FIN) AF: 0.390 AC: 4118 AN: 10572

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25433 AN: 67966

Other (OTH) AF: 0.380 AC: 804 AN: 2114

Alfa AF: 0.375 Hom.: 37147

Bravo AF: 0.320

Asia WGS AF: 0.458 AC: 1596 AN: 3478

EpiCase AF: 0.391

EpiControl AF: 0.397

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.8
DANN	Benign	0.83
PhyloP100		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.9
Mutation Taster		=99/1	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: rs749671; hg19: chr16-31088347; COSMIC: COSV56217640; COSMIC: COSV56217640;