rs12415791

chr10-30980182-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001143768.2(ZNF438):c.-192+4187G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00231 in 150,176 control chromosomes in the GnomAD database, including 9 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 0.0023 (9 hom., cov: 31)
• Consequence: ZNF438 NM_001143768.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400

Genes affected

ZNF438 (HGNC:21029): (zinc finger protein 438) Enables DNA-binding transcription factor activity. Involved in negative regulation of transcription, DNA-templated. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00231 (347/150176) while in subpopulation EAS AF= 0.0186 (95/5118). AF 95% confidence interval is 0.0155. There are 9 homozygotes in gnomad4. There are 166 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF438	NM_001143768.2	c.-192+4187G>A		intron_variant		ENST00000436087.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF438	ENST00000436087.7	c.-192+4187G>A		intron_variant		5	NM_001143768.2	A2

Frequencies

GnomAD3 genomes AF: 0.00229 AC: 343 AN: 150060 Hom.: 8 Cov.: 31

Gnomad AFR AF: 0.000493

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0131

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.0185

Gnomad SAS AF: 0.00376

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000885

Gnomad OTH AF: 0.000480

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

GnomAD4 genome AF: 0.00231 AC: 347 AN: 150176 Hom.: 9 Cov.: 31 AF XY: 0.00227 AC XY: 166 AN XY: 73114

Gnomad4 AFR AF: 0.000491

Gnomad4 AMR AF: 0.0133

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.0186

Gnomad4 SAS AF: 0.00376

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000885

Gnomad4 OTH AF: 0.000475

Alfa AF: 0.00257 Hom.: 1

Bravo AF: 0.00445

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.9
Dann	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs12415791; hg19: chr10-31269111;