rs201719725

Positions:

• chr18-74635297-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_017757.3(ZNF407):​c.4278G>A​(p.Leu1426=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00339 in 1,614,024 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0021 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0035 (11 hom.)
• Consequence: ZNF407 NM_017757.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.98

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 18-74635297-G-A is Benign according to our data. Variant chr18-74635297-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 212670.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.98 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF407	NM_017757.3	c.4278G>A	p.Leu1426=	synonymous_variant	2/9	ENST00000299687.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF407	ENST00000299687.10	c.4278G>A	p.Leu1426=	synonymous_variant	2/9	1	NM_017757.3	P2
ZNF407	ENST00000577538.5	c.4278G>A	p.Leu1426=	synonymous_variant	1/7	2		A2
ZNF407	ENST00000309902.10	c.4278G>A	p.Leu1426=	synonymous_variant	1/4	2
ZNF407	ENST00000582337.5	c.4278G>A	p.Leu1426=	synonymous_variant	2/5	5

Frequencies

GnomAD3 genomes AF: 0.00214 AC: 326 AN: 152206 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00414

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00223 AC: 555 AN: 249166 Hom.: 0 AF XY: 0.00202 AC XY: 273 AN XY: 135184

Gnomad AFR exome AF: 0.000517

Gnomad AMR exome AF: 0.000985

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00125

Gnomad NFE exome AF: 0.00420

Gnomad OTH exome AF: 0.00198

GnomAD4 exome AF: 0.00352 AC: 5150 AN: 1461700 Hom.: 11 Cov.: 41 AF XY: 0.00334 AC XY: 2431 AN XY: 727130

Gnomad4 AFR exome AF: 0.000627

Gnomad4 AMR exome AF: 0.00103

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00193

Gnomad4 NFE exome AF: 0.00432

Gnomad4 OTH exome AF: 0.00285

GnomAD4 genome AF: 0.00214 AC: 326 AN: 152324 Hom.: 1 Cov.: 33 AF XY: 0.00200 AC XY: 149 AN XY: 74496

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.000980

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00122

Gnomad4 NFE AF: 0.00414

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00332 Hom.: 0

Bravo AF: 0.00198

EpiCase AF: 0.00240

EpiControl AF: 0.00243

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 01, 2018

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	6.1
DANN	Benign	0.69

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: rs201719725; hg19: chr18-72347253; COSMIC: COSV55258443;