11-46701181-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_024741.3(ZNF408):c.52+82T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 1,609,898 control chromosomes in the GnomAD database, including 804,735 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 1.0 (76040 hom., cov: 30)
  • Exomes 𝑓: 1.0 (728695 hom.)
• Consequence: ZNF408 NM_024741.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.497

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-46701181-T-C is Benign according to our data. Variant chr11-46701181-T-C is described in ClinVar as [Benign]. Clinvar id is 1274687.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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
ZNF408	NM_024741.3	c.52+82T>C		intron_variant		ENST00000311764.3
ZNF408	NM_001184751.2	c.28+40T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF408	ENST00000311764.3	c.52+82T>C		intron_variant		1	NM_024741.3	P1
ZNF408	ENST00000526410.1	n.69+82T>C		intron_variant, non_coding_transcript_variant		3
ZNF408	ENST00000531866.1	n.70+82T>C		intron_variant, non_coding_transcript_variant		2
ZNF408	ENST00000534481.1			upstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.999 AC: 152060 AN: 152158 Hom.: 75981 Cov.: 30

Gnomad AFR AF: 0.998

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

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: 1.00

GnomAD3 exomes AF: 1.00 AC: 244914 AN: 244966 Hom.: 122431 AF XY: 1.00 AC XY: 133122 AN XY: 133136

Gnomad AFR exome AF: 0.997

Gnomad AMR exome AF: 1.00

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: 1.00

GnomAD4 exome AF: 1.00 AC: 1457506 AN: 1457622 Hom.: 728695 Cov.: 32 AF XY: 1.00 AC XY: 725263 AN XY: 725308

Gnomad4 AFR exome AF: 0.997

Gnomad4 AMR exome AF: 1.00

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: 1.00

GnomAD4 genome AF: 0.999 AC: 152178 AN: 152276 Hom.: 76040 Cov.: 30 AF XY: 0.999 AC XY: 74412 AN XY: 74454

Gnomad4 AFR AF: 0.998

Gnomad4 AMR AF: 1.00

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: 1.00

Alfa AF: 1.00 Hom.: 14471

Bravo AF: 0.999

Asia WGS AF: 1.00 AC: 3478 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.6
Dann	Benign	0.56

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: rs4752928; hg19: chr11-46722731;