rs7157322

Variant names:

• chr14-95116207-A-C
• rs7157322
• NM_177438.3:c.1752+246T>G

Your query was ambiguous. Multiple possible variants found:

• chr14-95116207-A-C
• chr14-95116207-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_177438.3(DICER1):​c.1752+246T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 152,068 control chromosomes in the GnomAD database, including 16,004 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.43 (16004 hom., cov: 32)
• Consequence: DICER1 NM_177438.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.582
• Publications: 4 publications found

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]

DICER1 Gene-Disease associations (from GenCC):

• DICER1-related tumor predisposition

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• pleuropulmonary blastoma

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• DICER1 syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 14-95116207-A-C is Benign according to our data. Variant chr14-95116207-A-C is described in ClinVar as Benign. ClinVar VariationId is 676815.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177438.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DICER1	NM_177438.3	MANE Select	c.1752+246T>G		intron	N/A	NP_803187.1	Q9UPY3-1
	DICER1	NM_001271282.3		c.1752+246T>G		intron	N/A	NP_001258211.1	Q9UPY3-1
	DICER1	NM_001291628.2		c.1752+246T>G		intron	N/A	NP_001278557.1	Q9UPY3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DICER1	ENST00000343455.8	TSL:1 MANE Select	c.1752+246T>G		intron	N/A	ENSP00000343745.3	Q9UPY3-1
	DICER1	ENST00000393063.6	TSL:1	c.1752+246T>G		intron	N/A	ENSP00000376783.1	Q9UPY3-1
	DICER1	ENST00000527414.5	TSL:1	c.1752+246T>G		intron	N/A	ENSP00000435681.1	Q9UPY3-1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64975 AN: 151950 Hom.: 15963 Cov.: 32

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.428 AC: 65076 AN: 152068 Hom.: 16004 Cov.: 32 AF XY: 0.423 AC XY: 31471 AN XY: 74346

African (AFR) AF: 0.689 AC: 28589 AN: 41464

American (AMR) AF: 0.360 AC: 5505 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1311 AN: 3472

East Asian (EAS) AF: 0.418 AC: 2159 AN: 5160

South Asian (SAS) AF: 0.232 AC: 1117 AN: 4818

European-Finnish (FIN) AF: 0.318 AC: 3360 AN: 10576

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21796 AN: 67972

Other (OTH) AF: 0.414 AC: 874 AN: 2110

Alfa AF: 0.345 Hom.: 5106

Bravo AF: 0.443

Asia WGS AF: 0.334 AC: 1163 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.49
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7157322; hg19: chr14-95582544;