rs1618523

Variant names:

• chr8-144840646-C-T
• rs1618523
• NM_003416.4:c.248-709C>T

Variant summary

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

The NM_003416.4(ZNF7):​c.248-709C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 151,814 control chromosomes in the GnomAD database, including 9,657 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 0.35 (9657 hom., cov: 33)
• Consequence: ZNF7 NM_003416.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 8 publications found

Genes affected

ZNF7 (HGNC:13139): (zinc finger protein 7) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be integral component of membrane. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

COMMD5 (HGNC:17902): (COMM domain containing 5) Predicted to be involved in proximal tubule morphogenesis. Located in cytosol and nucleoplasm. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF7	NM_003416.4	c.248-709C>T		intron_variant	Intron 4 of 4	ENST00000532777.6	NP_003407.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF7	ENST00000532777.6	c.248-709C>T		intron_variant	Intron 4 of 4	1	NM_003416.4	ENSP00000432641.2

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53822 AN: 151698 Hom.: 9647 Cov.: 33

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.355 AC: 53866 AN: 151814 Hom.: 9657 Cov.: 33 AF XY: 0.353 AC XY: 26160 AN XY: 74190

African (AFR) AF: 0.372 AC: 15410 AN: 41386

American (AMR) AF: 0.277 AC: 4230 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1390 AN: 3470

East Asian (EAS) AF: 0.322 AC: 1654 AN: 5136

South Asian (SAS) AF: 0.457 AC: 2202 AN: 4822

European-Finnish (FIN) AF: 0.338 AC: 3567 AN: 10544

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24238 AN: 67884

Other (OTH) AF: 0.334 AC: 701 AN: 2098

Alfa AF: 0.363 Hom.: 1248

Bravo AF: 0.349

Asia WGS AF: 0.440 AC: 1528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.68
DANN	Benign	0.32
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: rs1618523; hg19: chr8-146066031;