rs2446024

Positions:

• chr10-96133669-G-A
• chr10-96133669-G-C

Variant summary

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

The NM_001330736.2(ZNF518A):​c.-302+21G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 152,176 control chromosomes in the GnomAD database, including 60,511 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 0.89 (60510 hom., cov: 31)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: ZNF518A NM_001330736.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.605

Genes affected

ZNF518A (HGNC:29009): (zinc finger protein 518A) The protein encoded by this gene is a member of the krueppel C2H2-type zinc finger protein family. The encoded protein contains five zinc fingers and is likely a nuclear transcriptional regulator. Numerous transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Aug 2016]

LOC124902486 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF518A	NM_001330736.2	c.-302+21G>A		intron_variant		ENST00000316045.10
LOC124902486	XR_007062254.1	n.15061C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF518A	ENST00000316045.10	c.-302+21G>A		intron_variant		1	NM_001330736.2	P1

Frequencies

GnomAD3 genomes AF: 0.889 AC: 135133 AN: 152056 Hom.: 60468 Cov.: 31

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.934

Gnomad AMR AF: 0.860

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.957

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.953

Gnomad OTH AF: 0.893

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.889 AC: 135237 AN: 152174 Hom.: 60510 Cov.: 31 AF XY: 0.888 AC XY: 66081 AN XY: 74402

Gnomad4 AFR AF: 0.781

Gnomad4 AMR AF: 0.860

Gnomad4 ASJ AF: 0.892

Gnomad4 EAS AF: 0.867

Gnomad4 SAS AF: 0.853

Gnomad4 FIN AF: 0.957

Gnomad4 NFE AF: 0.953

Gnomad4 OTH AF: 0.895

Alfa AF: 0.908 Hom.: 10882

Bravo AF: 0.877

Asia WGS AF: 0.878 AC: 3054 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.4
DANN	Benign	0.33

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: rs2446024; hg19: chr10-97893426;