chr19-21370388-G-A

Variant names:

• chr19-21370388-G-A
• rs2127407
• NM_001355237.2:c.97-4850G>A

Variant summary

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

The NM_001355237.2(ZNF738):​c.97-4850G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 151,944 control chromosomes in the GnomAD database, including 24,591 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 0.57 (24591 hom., cov: 32)
• Consequence: ZNF738 NM_001355237.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 5 publications found

Genes affected

ZNF738 (HGNC:32469): (zinc finger protein 738) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in protein polyubiquitination. Predicted to be located 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=-0.57).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001355237.2. 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
	ZNF738	NM_001355237.2	MANE Select	c.97-4850G>A		intron	N/A	NP_001342166.1
	ZNF738	NM_001355239.2		c.97-4850G>A		intron	N/A	NP_001342168.1
	ZNF738	NM_001355240.2		c.97-4850G>A		intron	N/A	NP_001342169.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF738	ENST00000683779.1	MANE Select	c.97-4850G>A		intron	N/A	ENSP00000507366.1
	ZNF738	ENST00000311015.7	TSL:1	c.97-4850G>A		intron	N/A	ENSP00000311957.3
	ZNF738	ENST00000597810.5	TSL:3	c.97-4850G>A		intron	N/A	ENSP00000471336.1

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85913 AN: 151828 Hom.: 24580 Cov.: 32

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.566 AC: 85953 AN: 151944 Hom.: 24591 Cov.: 32 AF XY: 0.564 AC XY: 41903 AN XY: 74284

African (AFR) AF: 0.638 AC: 26445 AN: 41432

American (AMR) AF: 0.554 AC: 8456 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2127 AN: 3472

East Asian (EAS) AF: 0.631 AC: 3268 AN: 5178

South Asian (SAS) AF: 0.593 AC: 2859 AN: 4824

European-Finnish (FIN) AF: 0.494 AC: 5189 AN: 10512

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35701 AN: 67960

Other (OTH) AF: 0.591 AC: 1246 AN: 2110

Alfa AF: 0.556 Hom.: 3056

Bravo AF: 0.572

Asia WGS AF: 0.580 AC: 2010 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		0.25
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: rs2127407; hg19: chr19-21553190;