18-74631052-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_017757.3(ZNF407):c.33T>C(p.Asp11=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 1,610,846 control chromosomes in the GnomAD database, including 800,155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.99 (75160 hom., cov: 32)
  • Exomes 𝑓: 1.0 (724995 hom.)
• Consequence: ZNF407 NM_017757.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.86

Genes affected

ZNF407 (HGNC:19904): (zinc finger protein 407) This gene encodes a zinc finger protein whose exact function is not known. It may be involved in transcriptional regulation. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 18-74631052-T-C is Benign according to our data. Variant chr18-74631052-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 130821.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.87 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF407	NM_017757.3	c.33T>C	p.Asp11=	synonymous_variant	2/9	ENST00000299687.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF407	ENST00000299687.10	c.33T>C	p.Asp11=	synonymous_variant	2/9	1	NM_017757.3	P2
ZNF407	ENST00000577538.5	c.33T>C	p.Asp11=	synonymous_variant	1/7	2		A2
ZNF407	ENST00000309902.10	c.33T>C	p.Asp11=	synonymous_variant	1/4	2
ZNF407	ENST00000582337.5	c.33T>C	p.Asp11=	synonymous_variant	2/5	5

Frequencies

GnomAD3 genomes AF: 0.993 AC: 151174 AN: 152184 Hom.: 75112 Cov.: 32

Gnomad AFR AF: 0.998

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.941

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.991

GnomAD3 exomes AF: 0.986 AC: 242490 AN: 246028 Hom.: 119682 AF XY: 0.989 AC XY: 132106 AN XY: 133548

Gnomad AFR exome AF: 0.999

Gnomad AMR exome AF: 0.899

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.989

GnomAD4 exome AF: 0.997 AC: 1454017 AN: 1458544 Hom.: 724995 Cov.: 53 AF XY: 0.997 AC XY: 723598 AN XY: 725472

Gnomad4 AFR exome AF: 0.999

Gnomad4 AMR exome AF: 0.903

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.997

GnomAD4 genome AF: 0.993 AC: 151278 AN: 152302 Hom.: 75160 Cov.: 32 AF XY: 0.992 AC XY: 73910 AN XY: 74476

Gnomad4 AFR AF: 0.998

Gnomad4 AMR AF: 0.940

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.991

Alfa AF: 0.998 Hom.: 32484

Bravo AF: 0.988

Asia WGS AF: 0.993 AC: 3455 AN: 3478

EpiCase AF: 1.00

EpiControl AF: 1.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

not specified Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

-

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	0.030
Dann	Benign	0.36

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: rs7243081; hg19: chr18-72343008;