rs11878583

Variant names:

• chr19-51885293-A-G
• rs11878583
• NM_001370449.1:c.-219+1528T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370449.1(ZNF577):​c.-219+1528T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,098 control chromosomes in the GnomAD database, including 4,250 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 0.22 (4250 hom., cov: 32)
• Consequence: ZNF577 NM_001370449.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.924
• Publications: 12 publications found

Genes affected

ZNF577 (HGNC:28673): (zinc finger protein 577) 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. Predicted to be active 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370449.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF577	NM_001370449.1	MANE Select	c.-219+1528T>C		intron	N/A	NP_001357378.1	Q9BSK1-1
	ZNF577	NM_001370447.1		c.-219+1528T>C		intron	N/A	NP_001357376.1	Q9BSK1-1
	ZNF577	NM_001370448.1		c.-219+1528T>C		intron	N/A	NP_001357377.1	Q9BSK1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF577	ENST00000638348.2	TSL:2 MANE Select	c.-219+1528T>C		intron	N/A	ENSP00000491936.2	Q9BSK1-1
	ZNF577	ENST00000301399.12	TSL:1	c.-219+1528T>C		intron	N/A	ENSP00000301399.5	Q9BSK1-1
	ZNF577	ENST00000879657.1		c.-219+2551T>C		intron	N/A	ENSP00000549716.1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32723 AN: 151980 Hom.: 4242 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.215 AC: 32762 AN: 152098 Hom.: 4250 Cov.: 32 AF XY: 0.223 AC XY: 16613 AN XY: 74370

African (AFR) AF: 0.333 AC: 13792 AN: 41452

American (AMR) AF: 0.243 AC: 3712 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 684 AN: 3472

East Asian (EAS) AF: 0.300 AC: 1548 AN: 5164

South Asian (SAS) AF: 0.409 AC: 1972 AN: 4826

European-Finnish (FIN) AF: 0.197 AC: 2081 AN: 10570

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8409 AN: 68002

Other (OTH) AF: 0.218 AC: 459 AN: 2110

Alfa AF: 0.195 Hom.: 590

Bravo AF: 0.220

Asia WGS AF: 0.406 AC: 1410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.23
DANN	Benign	0.40
PhyloP100		-0.92
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: rs11878583; hg19: chr19-52388546;