rs148055528

Positions:

• chr11-46703166-CAGTGGTGACAGA-C
• chr11-46703166-CAGTGGTGACAGA-CAGTGGTGACAGAAGTGGTGACAGA

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4 BP6_Very_Strong BA1

The NM_024741.3(ZNF408):​c.581_592del​(p.Val194_Val197del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,611,622 control chromosomes in the GnomAD database, including 27,861 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2434 hom., cov: 30)
  • Exomes 𝑓: 0.16 (25427 hom.)
• Consequence: ZNF408 NM_024741.3 inframe_deletion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 3.10

Genes affected

ZNF408 (HGNC:20041): (zinc finger protein 408) The protein encoded by this gene contains ten tandem zinc fingers and an N-terminal SET domain, so it is likely a DNA binding protein that interacts with other proteins. In adults, the encoded protein is expressed most highly in retina. Consequently, defects in this gene have been associated with familial exudative vitreoretinopathy (FEVR) and retinitis pigmentosa (RP). [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_024741.3.
• BP6: Variant 11-46703166-CAGTGGTGACAGA-C is Benign according to our data. Variant chr11-46703166-CAGTGGTGACAGA-C is described in ClinVar as [Benign]. Clinvar id is 261760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-46703166-CAGTGGTGACAGA-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF408	NM_024741.3	c.581_592del	p.Val194_Val197del	inframe_deletion	4/5	ENST00000311764.3
ZNF408	NM_001184751.2	c.557_568del	p.Val186_Val189del	inframe_deletion	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF408	ENST00000311764.3	c.581_592del	p.Val194_Val197del	inframe_deletion	4/5	1	NM_024741.3	P1
ZNF408	ENST00000527008.1	n.458_469del		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21439 AN: 152094 Hom.: 2422 Cov.: 30

Gnomad AFR AF: 0.0309

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.0799

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.125

GnomAD3 exomes AF: 0.200 AC: 48794 AN: 243712 Hom.: 7521 AF XY: 0.193 AC XY: 25494 AN XY: 132162

Gnomad AFR exome AF: 0.0262

Gnomad AMR exome AF: 0.382

Gnomad ASJ exome AF: 0.0741

Gnomad EAS exome AF: 0.584

Gnomad SAS exome AF: 0.198

Gnomad FIN exome AF: 0.230

Gnomad NFE exome AF: 0.120

Gnomad OTH exome AF: 0.148

GnomAD4 exome AF: 0.160 AC: 234119 AN: 1459410 Hom.: 25427 AF XY: 0.161 AC XY: 116558 AN XY: 725970

Gnomad4 AFR exome AF: 0.0225

Gnomad4 AMR exome AF: 0.370

Gnomad4 ASJ exome AF: 0.0762

Gnomad4 EAS exome AF: 0.603

Gnomad4 SAS exome AF: 0.209

Gnomad4 FIN exome AF: 0.228

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.141 AC: 21454 AN: 152212 Hom.: 2434 Cov.: 30 AF XY: 0.151 AC XY: 11216 AN XY: 74396

Gnomad4 AFR AF: 0.0308

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.0799

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.122

Alfa AF: 0.128 Hom.: 245

Bravo AF: 0.139

Asia WGS AF: 0.310 AC: 1075 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Retinal dystrophy Benign:1

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs148055528; hg19: chr11-46724716;