rs6575499

Positions:

• chr14-95155863-T-C
• chr14-95155863-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_177438.3(DICER1):​c.-46+1367A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,160 control chromosomes in the GnomAD database, including 4,045 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 0.22 (4045 hom., cov: 33)
• Consequence: DICER1 NM_177438.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

Genes affected

DICER1 (HGNC:17098): (dicer 1, ribonuclease III) This gene encodes a protein possessing an RNA helicase motif containing a DEXH box in its amino terminus and an RNA motif in the carboxy terminus. The encoded protein functions as a ribonuclease and is required by the RNA interference and small temporal RNA (stRNA) pathways to produce the active small RNA component that represses gene expression. This protein also acts as a strong antiviral agent with activity against RNA viruses, including the Zika and SARS-CoV-2 viruses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2021]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DICER1	NM_177438.3	c.-46+1367A>G		intron_variant		ENST00000343455.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DICER1	ENST00000343455.8	c.-46+1367A>G		intron_variant		1	NM_177438.3	P1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33390 AN: 152042 Hom.: 4036 Cov.: 33

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.0412

Gnomad SAS AF: 0.0801

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.220 AC: 33437 AN: 152160 Hom.: 4045 Cov.: 33 AF XY: 0.214 AC XY: 15913 AN XY: 74388

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.0412

Gnomad4 SAS AF: 0.0806

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.234

Alfa AF: 0.138 Hom.: 312

Bravo AF: 0.223

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.52
DANN	Benign	0.72

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: rs6575499; hg19: chr14-95622200;