chr19-44495114-G-A

Variant names:

• chr19-44495114-G-A
• rs3786501
• NM_001278509.3:c.51+2170C>T

Variant summary

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

The NM_001278509.3(ZNF180):​c.51+2170C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 151,972 control chromosomes in the GnomAD database, including 8,032 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 0.31 (8032 hom., cov: 32)
• Consequence: ZNF180 NM_001278509.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.37
• Publications: 6 publications found

Genes affected

ZNF180 (HGNC:12970): (zinc finger protein 180) Zinc finger proteins have been shown to interact with nucleic acids and to have diverse functions. The zinc finger domain is a conserved amino acid sequence motif containing 2 specifically positioned cysteines and 2 histidines that are involved in coordinating zinc. Kruppel-related proteins form 1 family of zinc finger proteins. See MIM 604749 for additional information on zinc finger proteins.[supplied by OMIM, Jul 2002]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278509.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF180	NM_001278509.3	MANE Select	c.51+2170C>T		intron	N/A	NP_001265438.2
	ZNF180	NM_013256.7		c.132+2170C>T		intron	N/A	NP_037388.3
	ZNF180	NM_001288759.4		c.129+2170C>T		intron	N/A	NP_001275688.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF180	ENST00000592529.6	TSL:2 MANE Select	c.51+2170C>T		intron	N/A	ENSP00000468021.1
	ZNF180	ENST00000221327.8	TSL:1	c.132+2170C>T		intron	N/A	ENSP00000221327.3
	ZNF180	ENST00000590088.5	TSL:1	n.137+2170C>T		intron	N/A	ENSP00000468523.1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46676 AN: 151854 Hom.: 7999 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.308 AC: 46755 AN: 151972 Hom.: 8032 Cov.: 32 AF XY: 0.308 AC XY: 22914 AN XY: 74280

African (AFR) AF: 0.443 AC: 18320 AN: 41394

American (AMR) AF: 0.377 AC: 5756 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 985 AN: 3470

East Asian (EAS) AF: 0.402 AC: 2075 AN: 5156

South Asian (SAS) AF: 0.297 AC: 1428 AN: 4816

European-Finnish (FIN) AF: 0.187 AC: 1981 AN: 10574

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15305 AN: 67972

Other (OTH) AF: 0.300 AC: 631 AN: 2106

Alfa AF: 0.299 Hom.: 1453

Bravo AF: 0.329

Asia WGS AF: 0.393 AC: 1369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.014
DANN	Benign	0.52
PhyloP100		-3.4
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: rs3786501; hg19: chr19-44999175;