rs4801273

Positions:

• chr19-58488906-A-G

Variant summary

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

The NM_001304453.1(ZNF446):​c.803-384A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 150,354 control chromosomes in the GnomAD database, including 19,882 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 0.50 (19882 hom., cov: 28)
• Consequence: ZNF446 NM_001304453.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.840

Genes affected

ZNF446 (HGNC:):

SLC27A5 (HGNC:10999): (solute carrier family 27 member 5) The protein encoded by this gene is an isozyme of very long-chain acyl-CoA synthetase (VLCS). It is capable of activating very long-chain fatty-acids containing 24- and 26-carbons. It is expressed in liver and associated with endoplasmic reticulum but not with peroxisomes. Its primary role is in fatty acid elongation or complex lipid synthesis rather than in degradation. This gene has a mouse ortholog. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF446	NM_001304453.1	c.803-384A>G		intron_variant			NP_001291382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC27A5	ENST00000595851.5	c.*22-5260T>C		intron_variant, NMD_transcript_variant		2		ENSP00000469512

Frequencies

GnomAD3 genomes AF: 0.503 AC: 75566 AN: 150236 Hom.: 19857 Cov.: 28

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.503 AC: 75633 AN: 150354 Hom.: 19882 Cov.: 28 AF XY: 0.497 AC XY: 36475 AN XY: 73344

Gnomad4 AFR AF: 0.656

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.447

Alfa AF: 0.464 Hom.: 17313

Bravo AF: 0.503

Asia WGS AF: 0.401 AC: 1395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4801273; hg19: chr19-59000273;