rs10519280

Variant names:

• chr15-80100347-A-G
• rs10519280
• NM_019006.4:c.-18+1769A>G

Variant summary

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

The NM_019006.4(ZFAND6):​c.-18+1769A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0477 in 152,298 control chromosomes in the GnomAD database, including 250 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 0.048 (250 hom., cov: 32)
• Consequence: ZFAND6 NM_019006.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53
• Publications: 8 publications found

Genes affected

ZFAND6 (HGNC:30164): (zinc finger AN1-type containing 6) Predicted to enable polyubiquitin modification-dependent protein binding activity. Involved in cellular response to tumor necrosis factor; negative regulation of apoptotic process; and regulation of I-kappaB kinase/NF-kappaB signaling. Predicted to be located in cytosol. [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=-0.6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFAND6	NM_019006.4	c.-18+1769A>G		intron_variant	Intron 2 of 6	ENST00000261749.11	NP_061879.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFAND6	ENST00000261749.11	c.-18+1769A>G		intron_variant	Intron 2 of 6	1	NM_019006.4	ENSP00000261749.6

Frequencies

GnomAD3 genomes AF: 0.0477 AC: 7259 AN: 152180 Hom.: 250 Cov.: 32

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0333

Gnomad ASJ AF: 0.0547

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0130

Gnomad FIN AF: 0.0661

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0753

Gnomad OTH AF: 0.0482

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

GnomAD4 genome AF: 0.0476 AC: 7257 AN: 152298 Hom.: 250 Cov.: 32 AF XY: 0.0467 AC XY: 3474 AN XY: 74468

African (AFR) AF: 0.0123 AC: 512 AN: 41564

American (AMR) AF: 0.0332 AC: 508 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0547 AC: 190 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.0128 AC: 62 AN: 4826

European-Finnish (FIN) AF: 0.0661 AC: 701 AN: 10610

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0753 AC: 5123 AN: 68020

Other (OTH) AF: 0.0477 AC: 101 AN: 2116

Alfa AF: 0.0616 Hom.: 638

Bravo AF: 0.0442

Asia WGS AF: 0.00578 AC: 20 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	10
DANN	Benign	0.92
PhyloP100		1.5
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: rs10519280; hg19: chr15-80392689;