chr15-80076521-T-A

Variant names:

• chr15-80076521-T-A
• rs1357335
• NM_019006.4:c.-181+16712T>A

Variant summary

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

The NM_019006.4(ZFAND6):​c.-181+16712T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 152,044 control chromosomes in the GnomAD database, including 26,592 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 0.57 (26592 hom., cov: 32)
• Consequence: ZFAND6 NM_019006.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.906
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFAND6	NM_019006.4	c.-181+16712T>A		intron_variant	Intron 1 of 6	ENST00000261749.11	NP_061879.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFAND6	ENST00000261749.11	c.-181+16712T>A		intron_variant	Intron 1 of 6	1	NM_019006.4	ENSP00000261749.6

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87351 AN: 151924 Hom.: 26595 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.0908

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.622

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.575 AC: 87382 AN: 152044 Hom.: 26592 Cov.: 32 AF XY: 0.568 AC XY: 42232 AN XY: 74318

African (AFR) AF: 0.439 AC: 18213 AN: 41456

American (AMR) AF: 0.609 AC: 9290 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2227 AN: 3468

East Asian (EAS) AF: 0.0912 AC: 473 AN: 5188

South Asian (SAS) AF: 0.547 AC: 2635 AN: 4820

European-Finnish (FIN) AF: 0.609 AC: 6441 AN: 10578

Middle Eastern (MID) AF: 0.630 AC: 184 AN: 292

European-Non Finnish (NFE) AF: 0.680 AC: 46198 AN: 67970

Other (OTH) AF: 0.586 AC: 1239 AN: 2114

Alfa AF: 0.625 Hom.: 3366

Bravo AF: 0.566

Asia WGS AF: 0.351 AC: 1224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.1
DANN	Benign	0.84
PhyloP100		0.91
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: rs1357335; hg19: chr15-80368863;