19-56524993-A-G

Variant names:

• chr19-56524993-A-G
• rs45487092
• NM_020813.4:c.926A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000593197.1(ZNF471):​n.218-707A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00476 in 1,614,162 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0050 (37 hom.)
• Consequence: ZNF471 ENST00000593197.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.01
• Publications: 9 publications found

Genes affected

ZNF471 (HGNC:23226): (zinc finger protein 471) 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 by RNA polymerase II. 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 (MetaRNN=0.0075204074).
• BP6: Variant 19-56524993-A-G is Benign according to our data. Variant chr19-56524993-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2650562.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 37 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF471	NM_020813.4	c.926A>G	p.Gln309Arg	missense_variant	Exon 5 of 5	ENST00000308031.10	NP_065864.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF471	ENST00000308031.10	c.926A>G	p.Gln309Arg	missense_variant	Exon 5 of 5	1	NM_020813.4	ENSP00000309161.4
ZNF471	ENST00000591537.5	c.505A>G	p.Arg169Gly	missense_variant	Exon 5 of 5	2		ENSP00000466224.1
ZNF471	ENST00000593197.1	n.218-707A>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.00271 AC: 412 AN: 152216 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00520

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00255 AC: 640 AN: 250924 AF XY: 0.00259

Gnomad AFR exome AF: 0.000863

Gnomad AMR exome AF: 0.000579

Gnomad ASJ exome AF: 0.000895

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00495

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00498 AC: 7278 AN: 1461828 Hom.: 37 Cov.: 36 AF XY: 0.00471 AC XY: 3427 AN XY: 727212

African (AFR) AF: 0.000866 AC: 29 AN: 33476

American (AMR) AF: 0.000649 AC: 29 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.000842 AC: 22 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000684 AC: 59 AN: 86248

European-Finnish (FIN) AF: 0.000318 AC: 17 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00622 AC: 6913 AN: 1111994

Other (OTH) AF: 0.00346 AC: 209 AN: 60394

GnomAD4 genome AF: 0.00270 AC: 412 AN: 152334 Hom.: 0 Cov.: 33 AF XY: 0.00230 AC XY: 171 AN XY: 74492

African (AFR) AF: 0.00101 AC: 42 AN: 41570

American (AMR) AF: 0.000523 AC: 8 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00520 AC: 354 AN: 68042

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00406 Hom.: 1

Bravo AF: 0.00261

TwinsUK AF: 0.00890 AC: 33

ALSPAC AF: 0.00856 AC: 33

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00523 AC: 45

ExAC AF: 0.00257 AC: 312

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00431

EpiControl AF: 0.00439

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ZNF471: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.019	T
M_CAP	Benign	0.00050	T
MetaRNN	Benign	0.0075	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.29	N
PhyloP100		2.0
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.053
Sift	Benign	0.17	T
Sift4G	Uncertain	0.045	D
Polyphen		0.0080	B
Vest4		0.10
MVP		0.40
MPC		0.21
ClinPred		1.0	D
GERP RS		3.1
Varity_R		0.18
gMVP		0.066
Mutation Taster		=99/1	polymorphism

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: rs45487092; hg19: chr19-57036362;