rs470337

Positions:

• chr18-76960319-T-C
• chr18-76960319-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001306089.2(ZNF236):​c.5243-360T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 152,170 control chromosomes in the GnomAD database, including 49,399 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 0.80 (49399 hom., cov: 32)
• Consequence: ZNF236 NM_001306089.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

Genes affected

ZNF236 (HGNC:13028): (zinc finger protein 236) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in cellular response to glucose stimulus. Predicted to be active in nucleus. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF236	NM_001306089.2	c.5243-360T>C		intron_variant		ENST00000320610.14	NP_001293018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF236	ENST00000320610.14	c.5243-360T>C		intron_variant		1	NM_001306089.2	ENSP00000322361	P1
ZNF236	ENST00000253159.12	c.5237-360T>C		intron_variant		1		ENSP00000253159
ZNF236	ENST00000543926.6	c.*642-360T>C		intron_variant, NMD_transcript_variant		1		ENSP00000444524

Frequencies

GnomAD3 genomes AF: 0.804 AC: 122266 AN: 152052 Hom.: 49389 Cov.: 32

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.878

Gnomad ASJ AF: 0.788

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.823

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

GnomAD4 genome AF: 0.804 AC: 122316 AN: 152170 Hom.: 49399 Cov.: 32 AF XY: 0.802 AC XY: 59626 AN XY: 74386

Gnomad4 AFR AF: 0.706

Gnomad4 AMR AF: 0.878

Gnomad4 ASJ AF: 0.788

Gnomad4 EAS AF: 0.796

Gnomad4 SAS AF: 0.805

Gnomad4 FIN AF: 0.813

Gnomad4 NFE AF: 0.845

Gnomad4 OTH AF: 0.820

Alfa AF: 0.837 Hom.: 67406

Bravo AF: 0.803

Asia WGS AF: 0.791 AC: 2751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.56

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: rs470337; hg19: chr18-74672275;