18-35376967-A-G

Variant names:

• chr18-35376967-A-G
• rs116303449
• NM_001322286.2:c.-73+311T>C

Variant summary

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

The NM_001322286.2(ZNF396):​c.-73+311T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.095 in 151,754 control chromosomes in the GnomAD database, including 2,257 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 0.095 (2257 hom., cov: 32)
• Consequence: ZNF396 NM_001322286.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.764
• Publications: 5 publications found

Genes affected

ZNF396 (HGNC:18824): (zinc finger protein 396) Enables protein heterodimerization activity; protein homodimerization activity; and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription, DNA-templated. Located in cytoplasm and 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF396	NM_001322286.2	c.-73+311T>C		intron_variant	Intron 1 of 3	ENST00000589332.7	NP_001309215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF396	ENST00000589332.7	c.-73+311T>C		intron_variant	Intron 1 of 3	1	NM_001322286.2	ENSP00000466500.1

Frequencies

GnomAD3 genomes AF: 0.0949 AC: 14394 AN: 151638 Hom.: 2257 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0364

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.00708

Gnomad SAS AF: 0.00998

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.00141

Gnomad OTH AF: 0.0676

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

GnomAD4 genome AF: 0.0950 AC: 14421 AN: 151754 Hom.: 2257 Cov.: 32 AF XY: 0.0928 AC XY: 6881 AN XY: 74144

African (AFR) AF: 0.327 AC: 13527 AN: 41386

American (AMR) AF: 0.0364 AC: 556 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 9 AN: 3468

East Asian (EAS) AF: 0.00710 AC: 36 AN: 5072

South Asian (SAS) AF: 0.00957 AC: 46 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.0342 AC: 10 AN: 292

European-Non Finnish (NFE) AF: 0.00141 AC: 96 AN: 67856

Other (OTH) AF: 0.0669 AC: 141 AN: 2108

Alfa AF: 0.0552 Hom.: 131

Bravo AF: 0.108

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.3
DANN	Benign	0.11
PhyloP100		-0.76
PromoterAI		-0.046	Neutral
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: rs116303449; hg19: chr18-32956931;